JS PD KB

α-Synuclein / aSyn / SNCA

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α-Synuclein / aSyn / SNCA

Synthesis layer over the canonical by-photo corpus. This page does not replace data/processed/markdown/by-photo/. Every substantive statement links back to a source note or canonical transcription. Where the source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Tier 1 only. This page narrates the 39 Tier 1 sources fixed by alpha-synuclein-source-boundary. The remaining 145 Tier 2 and 54 Tier 3 candidate sources (238 candidates total) are owned by a sibling topic synthesis or by a section page; they are linked from the Source Boundary / Delegation section, not re-narrated here. Tier 2 / Tier 3 stem inventories live on the boundary map.

Overview

This page collects the corpus’s α-synuclein evidence into one navigable synthesis. The aSyn material in the source document is structurally a long single-thread of inherited nav_path segments under Pipeline of GD & GBA-PD > Supplement > … aSyn … plus several free-standing program nav-roots (TAK-341 (MEDI1341), SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), aSyn programs), the Lewy-pathology entry (md), the Pipeline of PD aSyn-Antibody / aSyn-Vaccine rows (md, md, md), the MSA CSF aSyn in MSA axis (md), the inflammation aSyn splicing cross-reference (md), and the ShareFolder Mitochondria asyn and mitochondria > Evidence in sPD bridge (md). The 39 pages cover foundational biology, animal models, postmortem and Lewy pathology, Seed-Amplification Assay (SAA), antibody and vaccine programs, SNCA-knockdown programs, MSA cross-reference, and links into the four prior topic syntheses (Parkin, Inflammation, Mitochondria, Biomarkers-Outcomes, PET / Imaging) and the GBA-PD pilot.

Authoring Rules

  • No domain-knowledge corrections. The page reflects what the sources record, not what the field is “supposed” to say.
  • Uncertain Spans on the source page are preserved as uncertainty; numeric values, dose schedules, antibody clone IDs, residue ranges, and Korean inline annotations are not paraphrased.
  • The body of data/processed/markdown/by-photo/ is not modified.
  • No raw photos are staged; no new figure assets added; figure-bearing pages are linked rather than re-embedded (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md).
  • Tables on canonical pages are not re-quoted verbatim; the canonical link carries the table.
  • Tier 2 / Tier 3 sources are not re-narrated here; the boundary map and the owner topic page already cover them.

Source Boundary / Delegation

Tier definitions are fixed by alpha-synuclein-source-boundary. Counts on this page match the boundary map:

tiercounttreatment on this page
Tier 1 — α-synuclein-central39narrative axis sections + Source Table below
Tier 2 — aSyn as linking axis145delegated; linked, not re-narrated
Tier 3 — passing mention54delegated; linked from boundary map only
candidates238full discovery set (boundary map)

Delegation owners (Tier 2 sources that should be read in their sibling-topic synthesis rather than re-narrated here):

  • Parkin / PARKN GT / PINK-1 ↔ aSyn cross-talk: 14 Tier 2 sources → parkin, parkn-gt. See the boundary-map note that parkin records the PARKN GT decision matrix using aSyn pathology absence as a patient-selection criterion, which is a meaningful scope contradiction worth surfacing here.
  • Inflammation / NLRP3 / Pyroptosis / CAPS / C5aR1 / In Vivo strategy Katy / Havrda KOL: 24 Tier 2 sources → inflammation, nlrp3-inhibitor. The In Vivo strategy Katy cluster (20240722_183234, _183238, _183241) uses α-synuclein PFF as the seeding model; the Tier 1 NLRP3 page included here (md) is the aSyn splicing segment, not a redundant inflammation re-narrative.
  • Mitochondria (TRAP1, asyn-and-mitochondria, Magnetoencephalography / Maiko Tanaka / MIBG, mitophagy in vivo): 3 Tier 2 sources → mitochondria. The Tier 1 bridge 20240722_183436 is retained on the α-synuclein side because its first nav_path segment is ShareFolder and its central content is the asyn and mitochondria > Evidence in sPD bundle.
  • Biomarkers and Clinical Outcome Measures (NFL, RBD, Retina / Rob Rubens, MoCA, SCOPA-AUT, biomarkers, Synapse, Surrogate endpoint, Reference range): 15 Tier 2 sources → biomarkers-outcomes.
  • PET / Imaging (PET tracer / Chemistry PET / NHP / Parameters of PET ligand / Workflow): 6 Tier 2 sources → pet-imaging.
  • GBA-PD pilot (20240722_181748 through _181813, _182149, _182303, _182310, _182313): per-compound CSF total / phospho-aSyn and insoluble / proteinase-K-resistant aSyn readouts → gba-pd, gba-therapeutics, PR001, Ambroxol, Venglustat, Eliglustat.
  • Brain Bank / BioOrchestra biomarker-catalog cluster (20240722_182617 → 20240722_183115, plus _184200, _184203): Tier 2 catalog rows owned by brain-banks-postmortem (Cluster D, _182617–_182704, _184200, _184203) and bioorchestra-biomarker-catalog (Cluster C, _182708–_183115 minus _183050); the boundary map flags 20240722_182722 (Masuda-Suzukake α-syn fibrils, propagation / Braak / Cholinergic block) as a candidate for promotion if the body is re-checked. Not re-narrated on this page.
  • MSA cluster (9 Tier 2 sources under sections/msa): owned by msa (MSA whole-section synthesis). The MSA aSyn axis on this page owns the Tier 1 MSA > aSyn in MSA > CSF aSyn in MSA page (md); cohort, diagnosis, outcome-measure (UMSARS), pathology, subtype, and disease-modifying program inventory rows are narrated on msa and additionally indexed on msa and pipeline-msa.

Source Coverage

The 39 Tier 1 sources collapse to the following first-nav_path clusters (verbatim, including trailing typos when present):

nav root (first nav_path entry)sourcescovered axis
Pipeline of GD & GBA-PD28aSyn supplement chain (animal models, postmortem, SAA, antibodies, astrocytic, mutations SNCA, fragments, structure, KO, biobank); Lewy-pathology adjacent block; BioOrchestra aSyn (therapeutic) antibody cell
aSyn programs1Propagation Suppressor / Degrader umbrella program
SNCA BTV (HDO) (PFR-4067-100)1SNCA BTV / HDO program executive summary
SNCA ASO (WAVE)1SNCA ASO clinical plan
TAK-341 (MEDI1341)1TAK-341 / MEDI1341 clinical studies
α-Synuclein and Lewy pathology in Parkinson's disease1Lewy-pathology entry / Supplement Positive vs Negative
MSA1aSyn in MSA > CSF aSyn in MSA
Inflammation1NLRP3 > Neuronal > Caspase 1 > aSyn splicing
ShareFolder1Mitochondria asyn and mitochondria > Evidence in sPD
PDE1PIAS2 > Pipeline of PD > aSyn - Antibody
Pipeline of PD2aSyn - Antibody > aSyn - Small molecules; aSyn - Vaccine
total39

Across these 39 Tier 1 sources, the source-note frontmatter records 79 uncertain_span_count entries and 12 body-embedded figure assets — review surface area, not resolutions. Numeric totals match the boundary map (Tier 1: 79 uncertain spans, 12 embedded images across 39 pages).

Foundational Biology — Distribution / Expression / Function / Structure / Synapse / Turnover / Homology / KO / Safety

The Supplement chain bundles foundational α-synuclein biology under a long inherited-nav_path thread. Reading-order anchors:

  • Distribution and expression. α-Synuclein is “abundant in the nervous system under normal conditions”, “predominantly expressed in neurons”, and “preferentially localized to presynaptic terminals and possibly the nucleus”, with α-syn mainly localizes in glutamatergic terminals (Taguchi et al., 2016); in the young brain it is Terminal 위주 (soma 에는 조금) (Chu and Kordower, 2007) and in the elderly it Concentrate in soma (Chu and Kordower, 2007). The page also records that astrocyte don't express aSyn, that RBCs have massive amount of aSyn, and that More than 99% of the alpha-syn resides in the red blood cells (RBCs) with less than 1% of the total amount in the plasma, platelets and peripheral blood mononuclear cells. GTEx bulk- tissue SNCA violin-plot tissue inventory and the IB) Human α-syn basal levels in plasma 0.9 nM, α-syn basal levels in brain 0.093 nM card are on the same page (md).
  • Function (of normal aSyn) — DNA-damage / homology / in-vitro. The Supplement nav Function (of normal aSyn) > Grading/Scoring of LB pathology > Homology > In vitro studies of aSyn walks function and homology evidence in one page (md). The status-bar lead-in at the bottom of the prior page notes the 2019 Schaser line that aSyn is normally localized in the nucleus / When DNA damage occurs → serine-129 phosphorylated alpha-syn is rapidly recruited to DNA damage sites, and that Lewy inclusion-containing neurons in both mouse model and human-derived patient tissue demonstrate increased DSB levels (md).
  • Mutations SNCA and Neurodegeneration. Five capture-time-adjacent pages walk Mutations SNCA > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSyn. The first page preserves a trailing-... truncation in the nav_path itself (Neurodegeneration and aS...) — preserved verbatim (md) — and the chain continues at md, md, md, and md. All five carry low uncertain-span counts (≤1 each) and zero body-embedded figures.
  • Postmortem aSyn / Release / Safety / KO of α-syn / Seed-Amplification entry. Pipeline of GD & GBA-PD > Supplement > Postmortem aSyn > Release > Safety for aSyn > KO of α-syn > Seed-Amplification Assay walks the safety-of-knockdown thread and seeds the SAA section (md).
  • Skin aSyn / Sources / Species / Native conformation / Summary aSyn species. Single page covering peripheral biopsy sources of aSyn (md).
  • Fragments (Truncation) / Assay Truncation / Structure of aSyn. Three capture-time-adjacent pages walk Summary aSyn species > NDE > Fragments (Truncation) > Assay Truncation > Structure of aSyn (md, md, md). The Caspase-1 aSyn splicing paper (Ma 2018 #2046; Wang 2016 #2086) on md supplies the caspase-1 cleavage-site → α-Syn121 + C19 fragment biology that bridges this thread to the inflammation cluster.
  • Synapse and aSyn / TM for aSyn programs / Turnover of aSyn. Synapse and aSyn > TM for aSyn programs > Turnover of aSyn > ATP13A2 (Park9) walks turnover and TM-for-program rationale (md, md). The ATP13A2 (Park9) > BBB / disruption / opener > BD > Process / BeyondBio > Biobank page supplies the lysosomal-aSyn / Park9 entry (md).

Animal Models — Non-Spreading and Spreading

The aSyn animal-models band is a 6-page sequence under `Pipeline of GD & GBA-PD > Supplement > … aSyn > Animal models of aSyn

Non-Spreading Models > Spreading Models > Summary of a-syn animal models`.

  • Non-Spreading Models. Transgenic mice (KO and overexpression), grafting models, intracerebral protein injections, and virally induced expression. The main handicap of these models is that no significant nigrostriatal degeneration has been found in most of them, although some of these mice showed decreased striatal levels of TH or DA and behavioral impairments [80] (md). Per-line inventory: PDNG78 (PDGF promoter, retinal ganglion accumulation), Line 61 / Thy1-aSyn (extensive accumulation, neurodegeneration with loss of TH immunoreactivity in the striatum, plus the Takeda / QPS Line 61 PD mouse-model info card with α-synuclein levels by MSD), Wade-Martins SNCA BAC JAX 023837 (entire human SNCA gene under human promoter, Snca KO crossed; ~2-fold overexpression with age-dependent striatal neurotransmission deficits, loss of nigral DA neurons, and motor dysfunction), F28tg / F28Pka, Nussbaum PAC-Tg(SNCAWT) JAX 010710, and MJFF tools consortium 2022 Q3: failed for the human-aSyn-without-endogenous-mouse-aSyn line (md). Mutant PrP-A53T-SNCA TG (line M83) is the second-page anchor: develops a severe and complex motor impairment, leading to paralysis and death, and pathologically showed Lewy body-like inclusions … But no significant nigrostriatal degeneration, with cortical lysates showing decreased GBA activity (~80–90% residual; Rockenstein et al. 2016, PMID 27126635) and the dbl-PAC (SNCAA53T,Snca-/-) Prevail host. Mutant KI A53T-SNCA Rat (Tools Consortium / Sean Clark / Amicus, CRISPR-Cas9 generated; α-syn KO strain ID 10150 and α-syn A53T KI strain ID 10220 at Horizon Discovery) and the truncated MI2 TH-promoter line (1–120 α-syn) round out the inventory (md).
  • Spreading Models. PFFs and PFF + AAV-A53T spreading evidence, including the in-vivo evidence matrix (Desplats 2009, Hansen 2011, Bae 2014, Kordower 2008 / Li 2008 graft studies, Karampetsou 2017 Sci Reports pSer129 phosphorylation potentiation, Mason 2016 OB injection with cross-seeding species barrier, Sorrentino 2017 non-anatomically-connected spread, Recasens 2014 LB-extract NHP evidence). The Atuka NHP design — ① [day 1] Bilateral injection in SN of AAV-hA53T aSyn → ② [day 28] Bilateral Injection of PFFs derived from mouse … in striatum, 1 month later, in cynomolgus monkeys ~9 years of age — and the NHP results matrix (DAT 18F-FPCIT, VMAT2 18F-AV133, HPLC DA/DOPAC/HVA, TH stereology, 3T MRI, DTI, pSer129 histology, total/oligomer/seed CSF, t-Tau/p-Tau/Inflammatory BM) sit here (md, md).
  • Woodruff lab accelerated PFF model. a-syn of mouse / mouse / accelerated model: Motor deficits start around 1 months post PFF injection (4 month required for further progression) vs the [기존모델] a-syn of human (synthetic), into mouse striatum, Motor deficits start around 4 months post PFF injection (6-8 month required for further progression); (Gordon, 2018 #585) NLRP3i MCC950 single-injection PFF protocol with Caspase-1 / ASC ↑ at Day 30 and pS129 transmission Day 30–180 (md).
  • TAKEDA × Atuka lentivirus + α-syn tg mice. TAK-341 IDP plan: if TAK-341 is shown to reduce αSYN spreading in the NHP model and that reduction is predicted by suppression of CSF αSYN, the model is validated. Human PFFs injected on March 26, 2020 when Suzhou facility reopened after COVID; plasma, CSF, DAT/VMAT2 scans, and histopathology collected at 2 and 4 months post-injection (md).
  • Reference inventories. (Patterson 2019 #4581) bilateral mouse striatum PFF injection, (SNCA BAC tg mouse 10-day inoculation observation), (Yamakado 2012 #1460), (Volpicelli-Daley 2014 Acta Neuropathol #743 #1738), (Bru 2013 #1370) BAC mouse PD, spreading-models comparison table (PFF vs AAV mechanism / spreading direction / contralateral transmission / Tx aims), {Chung 2019} bilateral-pathology-from-unilateral caveat, and the Rey 2019 / 2018 / 2016 olfactory-bulb PFF rows (with Thioflavin-S-positive inclusions, prodromal-PD analogue, HuPFF vs mPFF spreading asymmetry) sit on md and md.
  • Vargas 2019 summary table and PFF preparation. Vargas et al. Ageing Research Reviews 50 (2019) 89–101 Table 1 — Summary of in vivo studies representing the major milestones in α-syn prion-like spreading, and the Transgenic vs Vector-mediated α-syn vs Injection comparison matrix (NHP available? / a-syn expression level / a-syn accumulation / aggregation / propagation / Neurodegeneration / Behavior). PFF preparation (37 °C with shaking for 7 days; storage only at –80 °C; sonication to ≤50 nm; in-vivo pilot validation required) is on the same page (md).
  • MOA of aSyn spreading. The axon-transport table — retrograde AT (Brundt 2012, Exosome / passive diffusion), antero & retro AT (Brahic 2016, exophagy / active endocytosis), GM1 lipid-raft association (Fortin 2004), MMP3 cleavage of secreted monomers, and Extracellular aSyn Activates microglia → kills DA neurons (Lee, 2008 #620) — also lives on md and continues into md.

Postmortem and Lewy Pathology

  • α-Synuclein and Lewy pathology in Parkinson's disease > Supplement Positive vs Negative is the canonical Lewy-pathology entry. The page reproduces the Kalia and Kalia genetic-PD vs Lewy-pathology Table 1 (SNCA, LRRK2, VPS35, EIF4G1, DNAJC13, CHCHD2, Parkin, PINK1, DJ-1, ATP13A2, FBXO7, GBA, PANK2, PLA2G6, SLC18A2, SPG11, SYNJ1, POLG1, RAB39B, 22q11.2), the small GBA / LB mini-table (GBA가 LB내에 있는 확률 75% (PD w GBA mutations) vs <10% (PD w/o GBA mutations)), the Supplement: Positive vs Negative Lysosomal-function / a-syn / Synapse contexts, and the upper portion of the 총정리 GBA protein & activity POSTMORTEM matrix (md).
  • a-syn POSTMORTEM under Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activity reproduces the Choi 2011 cerebral-cx fractionation matrix (TBS-soluble / SDS-soluble / urea-soluble × monomer / oligomer × normal / synopathy only / GBA mutation + synopathy / GBA mutation only), the Mazzulli 2011 / Murphy 2013 / Murphy 2014 postmortem rows, the a-syn SH-SY5Y + Cullen and a-syn PC only cell-line summaries, the FRACTIONATION protocol comparison, and the bottom Sidransky 2012 review opener (md).
  • Postmortem aSyn, Release, Safety for aSyn, KO of α-syn — (md, md).
  • CSF & Blood (a-syn). Two adjacent pages bundle the CSF-aSyn study comparison table — King 2022 #2779, Eusebi 2017 / 2015 #2331 / #2751, Chou 2014 #2751, Mollenhauer 2017 #2337 / 2016 #2336 / 2019 #2733 / 2742, Hall 2016 #2339 BioFinder, Hansson 2014 PMID 24987465 with the α-Synuclein oligomers / oligomers/total / total Table 1 (controls / PD / DLB / MSA, Number 98, Male/Female 35/63, Age 69 (11.6), MMSE 29 (28-30); oligomer values clipped at the right edge and preserved with trailing .. per Uncertain Spans), Compta 2015 #2637 (RBD / PDND / PDD oligomeric αSyn boxplot), Majbour 2021 DenoPa, van Steenoven 2018 VUMC, Schirinzi 2019 #615, Wang 2012 #1261, PD01A (ACI-7104) Volc 2020 #932 with Majbour’s Syn-O2 antibody motor-score r=0.515, Lin 2019 #1255 plasma pS129 / total aSyn (clipped underscore preserved as a ± placeholder), Chang 2019 #2739, Wang 2020 #1638, Chatterjee 2020 #1263, Yamashita 2023 #2740 review, Transpharmation Attyloid Blömeke 2022 #2639 sFIDA. The Js summary notes Oligomeric a-syn is much greater than total a-syn (about ?-fold) (the ? placeholder is preserved verbatim; quality_metrics.uncertain_span_count = 1 records the placeholder). The comparison page also records the MDS 2020 PD01A note that CSF total aSyn is mainly composed of monomeric aSyn (Mollenhauer 2017, PMID 28734051) and that “80 % of CSF composition (ie, proteins) derives from the filtration of peripheral blood, whereas 20 % derives from CNS cells” (md, md).
  • Astrocytic aSyn. “Astrocytic inclusions of αSyn are invariant features in PD and DLB but observed less frequently in MSA” plus the Aflaki 2020 #1141 GD1 / GD2 iAstrocyte GCase activity / GlcCer / GlcSph / cathepsin-D evidence (md, md).

Seed-Amplification Assay (SAA)

Pipeline of GD & GBA-PD > Supplement > Seed-Amplification Assay > Quantification > Utility > Sources of aSyn is the dedicated SAA nav-root, with Safety for aSyn > KO of α-syn > Seed-Amplification Assay > Quantification as the immediate predecessor and Sources of aSyn > Skin aSyn > Species > Native conformation > Summary aSyn species as the immediate successor in capture-time order (md, md, md, md). RT-QuIC and oligomer-detection cross-references appear on the antibodies page (MJFR-14-6-4-2, Syn-O2, 2A1, 3G7, 5G4, x122 a-syn antibody) at md. The MSA aSyn seed assays row is referenced under md (Atuka NHP CSF readout) and on the MSA page (md). RBD / prodromal SAA stratification is delegated to the biomarker-outcomes synthesis (biomarkers-outcomes RBD axis).

Antibody and Immunotherapy Programs

The corpus’s antibody / vaccine evidence is split between three Tier 1 program pages, three Tier 1 Pipeline-of-PD rows, and two Tier 1 supplement / cross-reference pages.

  • TAK-341 / MEDI1341 (Takeda / MedImmune). Program-level evidence package and Source Table now live on tak-341 (5 sources: 2 TAK-341 nav-rooted pages + 3 Pipeline-of-PD cross-pipeline pages). The axis below summarises the program in topic context; follow the entity for the full Evidence Package, Key Source Interpretations, and Uncertainties Carried From Source. PK/PD model — TAK-341 recognises an epitope at residues 102–130 in the C-terminal region of α-syn (MEDI1341 Investigator's Brochure: MEDI1341 recognizes an epitope located in the C-terminal region of the alpha-syn protein between amino acids 102 and 130. TAK-341 epitope is coded by exon 5 which is absent in the SNCA-112 and SNCA-98 isoforms, which constitute a sizeable fraction of total aSYN.). MEDI1341 is the only antibody without an effector function (aglycosylated IgG1; no FcγR / C1q recognition). KD for monomeric aSyn is 106 pM (Octet) / 74 pM (KinExA), with affinity for aggregated aSyn 37.3–930 pM (not substantially different than for monomeric). The Capture-Aggregate ELISA (Figure 4) plus the JS aside Does this mean that tak-341 has stronger affinity to aggregated aSyn than to monomer? It seems not. appear in body. The PK/PD model (two-compartment plasma / CSF–brain with Ksyn, Kon, Koff, Kdeg, Kint), Figure 18 predicted plasma profile and target-suppression curves, Table 6 Key PK/PD model parameters (incl. Human alpha-syn basal levels in plasma 0.9 nM, brain 0.093 nM, Human t1/2 of alpha-syn in plasma / brain 240 h, MEDI1341 brain penetration 0.1 %, MEDI1341 affinity 0.074 nM), and Table 7 Planned MEDI1341 dose escalations (Cohort 1 70 mg → Cohort 5 4200 mg) are on md. 4 body-embedded figure assets, 7 uncertain spans — review surface, see the page’s Uncertain Spans table for KD exponents, dose legends, and Cohort 2 / 3 visibility flags. Clinical-studies follow-up — SAD HV, MAD PD (Cohort 1 (1200 mg) / Cohort 2 (2400 mg) / Cohort 3 (4800 mg), N=12 per cohort (N=9 MEDI1341, N=3 placebo)), MSA Ph2 study (FPI in 202207, BM: NFL), the comparator Prasinezumab MAD row (↓ 96–97 % free aSyn at the highest dose; monomeric aSyn in CSF did not change (due to its low affinity to monomeric aSyn). At the time, Prothena had no assay for a-syn aggregates in CSF), the molarity / relative-concentration calculation (αSYN in CSF: 194.4 ng/L / MW 14500 → 1.34E-11 M (relative 6.19) ; 341 in CSF: 320.5 ng/L / MW 148000 → 2.17E-12 M (relative 1)), and the aSyn programs portfolio table opener live on md.
  • aSyn programs > aSyn Propagation Suppressor (umbrella) — Promoted to asyn-propagation-suppressor as of 2026-05-03; the program-level Evidence Package, Key Source Interpretations, Source Table, and Uncertainties Carried From Source live there. The Old Portfolio Entry milestone grid with cumulative cost (1 oku¥ → 30 oku¥) and cumulative time (1–2 yrs → 6.5–9.3 yrs), the aSyn Degrader patient-selection notes (DLB amygdala SPAL; heterogeneity PD vs MSA per Strohäker 2019 #1785), the aSyn Propagation Suppressor in-vitro models (Mouse primary cortical neurons (arnu) + (mouse) aSyn PFF; `(SNCA mutation-derived) iPS-Dopaminergic neuron
    • (mouse or human) aSyn PFF), the Expected MOA of HIT molecules pathway diagram (HSPGs / LAG3 / Receptor clustering / endosome / lysosome / LRRK2 / VPS35 / GBA / Exosome / Exocytosis / nanotube / PFF neuron with red callouts for Extracellular trap / Internalization inhibition / Aggregation inhibition / SNCA-α-syn reduction / Degradation enhancement / Secretion inhibition / Transmission inhibition), and the SM propagation suppressor vs αS mAb vs ASO/NAM differentiation tables on the same page ([md](/markdown/by-photo/20240722_181827.md)). embedded_image_count = 0`: figure-mixed crops are kept as evidence per the 2026-04-29 body-purity decision.
  • Pipeline of PD aSyn-Antibody / Small-molecules / Vaccine. Three Tier 1 pages cover the cross-pipeline antibody / small-molecule / vaccine inventory. md reproduces the eight-program aSyn-Antibody comparison row (Prasinezumab / Cinpanemab / TAK-341 (MEDI1341) / Lu AF82422 / ABBV-0805 / Affitope PD01A / Affitope PD03A / UB-312) with epitope and development-status columns, plus the α-syn sequence targeted by mAbs and vaccines diagram description with horizontal binding-range labels (Cinpanemab N-term, Prasinezumab, MEDI1341, Lu AF82422, ABBV-0805 C-term cluster, PD01A, UB-312 further C-term) and the Nitrase NITROME nitrated-α-synuclein program preclinical narrative. md extends this with the PASADENA Part 1 / Part 2 / Part 3 trial-design table (N=316, 1500 mg vs 4500 mg per body weight ≥65 kg / 3500 mg <65 kg, DaT-SPECT anchors, 80 % power for 37.5 % relative MDS-UPDRS Total change, results “did not meet the primary objective (MDS-UPDRS total score), but showed signals of efficacy (MDS-UPDRS, Part III)” with the JS contradiction note DaTScan changes showed no differences ... 밑에 MAD 등에서 보면 aSyn 줄이는 것 확실할텐데도 Datscan 과 연결 안 되는 point!), the Prothena/Roche prior P1 SAD/MAD CSF/serum ratio (0.3 %), the BIIB054 Cinpanemab P1 evidence (28-day half-life, CSF/serum ratio 0.2 %), the ABL301 (Sanofi / ABL Bio) Grabody-B bispecific data, the mAbs summary table, and the aSyn small-molecule rows (T100-18 A; UCB0599 / minzasolmin “ORCHESTRA” NCT04658186 P2 ; the visible-as-written drug-name token 200-11, 30599 (313), zasolmin /norvatis is preserved per the source’s Uncertain Spans). md extends this with the aSyn - Vaccine table (NPT200-11 Neuropore aS aggregation inhibitor; Anle138b MODAG/TEVA; Ionis; PD1601 / PD1602 BioArctic / AbbVie), the AC Immune PD01A (ACI-7104) and PD03A AFFiRiS active- immunotherapy program (P2 VacSYn / NCT06015841 adaptive design, P1 MSA / NCT02270489 with 89 % PD01-specific antibody response and PD03A 58 %, P1 NCT01568099 sPD with the 50 % Lowering of Pathological aSyn (Oligo-aSyn) in CSF result), the AFF008 study series figure (3 embedded image assets), the CSF Oligo-aSyn / MDS-UPDRS III correlation block (early reduction of CSF Oligo-aSyn correlated with longitudinal MDS-UPDRS III; PD01A-induced antibody titers correlated with stabilization of MDS-UPDRS III; r = 0.515 oligo-α-syn vs baseline MDS-UPDRS Part 3, p = 0.020), and the SAD-study MEDI1341 PK table (Dose increment / Cmax / DPF Cmax / AUC₀₋∞ / DPF AUC at 70 / 210 / 400 / 1200 mg).
  • SNCA ASO (WAVE). Promoted to snca-aso-wave as of 2026-05-03; the program-level Evidence Package, Key Source Interpretations, Source Table, and Uncertainties Carried From Source live there. SNCA ASO (WAVE) > Clinical plan of SNCA ASO records the SNCA ASO PK/PD relationship in transgenic mice (Single ICV, 100 µg, A53T SNCA mice → 1.2–1.9× better KD vs IONIS, 3.5–7.4× better exposure; per-tissue / per-clone t1/2 / IC50 / Imax / Projected KD at 8 weeks at 100 µg/g table for WV-36397 / WV-37643 / WV-39172 / WV-42827 in cortex and striatum), the Ph1b/2 design (IT, Early PD, 3–4 dose levels, Q monthly → Q3 m dosing; sentinel N=2 then N~4/arm, expansion to N~15/arm once PD effects on CSF aSyn are noted at ≤6 mo; POM will be informed by CSF aSyn. ePOC will be informed by NfL and DaT or VMAT2 imaging at ~ month 12.), the PET SNCA ASO biodistribution plan, the SNCA ASO question list (PD vs MSA, maximal KD safety, MOUSE/NHP translation, monomer / p-asyn / oligomeric KD, NDE, NHP spreading model used as go/no-go criterion), and the TAK-071 K-1-02 OC study (FPI 30 Nov 2020 / LPLV 27 Feb 2023; randomized, double-blind, placebo-controlled crossover; primary endpoint change in gait variability during a 2-minute walk on a 10-meter walkway; visible power table with cognition criterion d = 0.49 / 0.54) (md).
  • SNCA BTV (HDO) (PFR-4067-100). Promoted to snca-btv-hdo as of 2026-05-03; the program-level Evidence Package, Key Source Interpretations, Source Table, and Uncertainties Carried From Source live there. Executive summary (Ryouta Maeda) walks the LGE / PE / CN / CS / IND phase plan with 2018 (?) LGE marker, PE within FY2022 for IT and (deferred) BTV, Selected 18개 18mer ASO in vitro, 50 % KD (mRNA, at low dose to secure safety margin). Animal model TBD, But SNCA BAC TG (human WT aSyn) is unlikely b/c it does not show pathologic aSn, the Ryouta Maeda notes (SNCA mRNA in plasma NDE as TE marker similar to MAPT HDO PJ; oligomer aSyn over RT-QuIC; differentiation against Ionis’s BIIB101 / ION464 by KD potency in model mice; explanation of why the Wave collaboration was discontinued (“firewall”) and why MAPT HDO IT failed (technical IT issues at domestic CRO)), the 20230630 differentiation question list, the Translation table of aSyn readouts (mRNA KD across monomeric / phosphorylated / oligomeric forms, regional TfR1 PET, NDE mRNA, RT-QuIC, total aSyn CSF, ASYN PET (QST), retinal BM, MIBG, DATscan, Vmri for LBD), the HDO PET workflow (Step 1 PK study to compare plasma-to-brain ratio over time → terminate or proceed → Step 2 modification impact → Step 3 rodent PET protocol → Step 4 preclinical species translation), and the four Paul McQuade technical questions for HDO PET feasibility (md). The page’s SharePoint URL is preserved verbatim because SCNA/SNCA, percent-encoding, and the long View token are visually ambiguous.
  • aSyn (therapeutic) antibody — the BioOrchestra-cluster page records {Trudler, 2021 #2028} hiPSC-derived microglia: aSyn-antibody complexes enhanced rather than suppressed inflammasome-mediated IL-1β secretion, alongside the Comorbidity (RA / NSAID / DM / CVD / Obesity) and Summary (sento M) tables that frame BBB-crossing cytokines and IL-1β-PD-prevalence questions. The page is bucketed under sections/gba-pd-asyn in the boundary map but its first nav_path segment is Pipeline of GD & GBA-PD > Supplement > … BioOrchestra > Inflammation > ALS > aSyn (therapeutic) antibody > Comorbidity (md).
  • Antibodies to aSyn — the per-antibody host / Species / epitope matrix (A11, OC, SNL1 / SNL4, LB509, C20, 81A, Syn-1 / 03 / 202 / 204 / 205 / 208 / 211 / 303 / 506, EP1536Y, 610787, Syn1150, D37A6, MJFR1, Syn-O2, MJFR-14-6-4-2, 2A1, 3G7, 4D6, 5C2, 5G4, x122) plus the Pathologic-conversion / Pathological-aggregation conformer matrix and the Vaikath 2019 #1599 Pan-Syn / N-1&2 / NAC / NAC-1&2 / Syn-1 / NACP-C / Hu-Syn / 140 / 95 / A53T / A30P fragment map are on md. The page also notes current Abs can't distinguish physiological (HC) between pathological species (PD pts) as a flagged limitation.

SNCA-Knockdown Programs (umbrella)

The umbrella view across the three knockdown / silencing program nav-roots — TAK-341 (antibody), SNCA ASO (WAVE) (RNase-H ASO), SNCA BTV / HDO (PFR-4067-100) (BTV-conjugated heteroduplex oligonucleotide), and aSyn programs > aSyn Propagation Suppressor (small-molecule phenotypic-screen umbrella incl. aSyn Degrader) — is laid out on the aSyn-programs entry-point (md) with the SM propagation suppressor vs αS mAb vs ASO/NAM differentiation table. Cross-pipeline competitor inventory is on md and md. TAK-341 / MEDI1341 has been promoted to tak-341, SNCA BTV (HDO) / PFR-4067-100 has been promoted to snca-btv-hdo, SNCA ASO (WAVE) has been promoted to snca-aso-wave, and the aSyn programs umbrella (aSyn Propagation Suppressor / aSyn Degrader) has been promoted to asyn-propagation-suppressor as of 2026-05-03; the program-level Evidence Packages, Key Source Interpretations, Source Tables, and Uncertainties Carried From Source live on those entity pages. All four aSyn-cluster program nav-roots in the corpus now have dedicated entity pages.

MSA aSyn

The MSA cluster’s whole-section synthesis lives at msa; this α-synuclein page only owns the Tier 1 MSA > aSyn in MSA > CSF aSyn in MSA page anchored on 20240722_184156. That page bundles Booth 2015 #1745 MRI in PD and MRS in PD reviews; the Animal models of MSA table — (PLP)-hα-syn transgenic mouse (Poewe MSA model), M2 mice (CNP)-hα-syn, viral-based oligodendrocyte α-syn animal models in rats and NHPs, the Cre-loxP adult-onset model, MBP-aSyn mouse (Ubhi 2010), and the Hasegawa 2016 brain-homogenate-into-mouse note that “Mice injected with MSA brain homogenate develop neuronal a-syn pathology, but not in oligodendrocytes”; the Brain aSyn in MSA table — {Schweighauser, 2020 #2060} α-syn filament cores extending residues 30–100, GCI α-syn ~1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation per {Peng, 2018 #2062}, {Prusiner, 2015 #2063} inoculation of MSA but not PD aggregates inducing pSer129 deposition, and the Solubility in SDS distinguishes a-syn filaments of MSA from those of DLB (44). note; and the CSF aSyn in MSA table — the JS summary CSF aSyn 은 MSA 에서 정상과 차이가 없고, exosome aSyn 은 결과가 inconsistent 하니, 유용없으나, tak-341 의 response 로서 감소를 보는 의미는 있겠다., {Ateno, 2012 #1467} Control / AD / DLB / PD / MSA boxplot, {Mavroudis, 2020 #1468}, {ga, 2018 #1623} review noting six of nine antemortem-CSF studies showed ↓ total α-syn in MSA vs controls and three did not, and {ulds, 2012 #2455} 76 Postmortem opener (clipped at the bottom edge) (md). MSA program / disease-modifying / cohort / diagnosis / outcome-measure / pathology / subtype inventory rows are delegated to msa, with the section index at msa and the nav-root index at pipeline-msa.

Caspase-1 / Inflammation aSyn splicing Cross-Reference

Inflammation > NLRP3 > Neuronal > Caspase 1 > aSyn splicing > Catalytic cleft is the only Tier 1 inflammation page; its content sits inside the inflammation section’s NLRP3 sub-tree but its central body is the {Ma, 2018 #2046} Caspase-1 cleaves full-length α-Syn to generate α-Syn121 and the {Wang, 2016 #2086} MALDI-TOF cleavage-site identification (Asp121, MW 13167 Da; D121E abolishes truncation; VX765 inhibits aSyn truncation; Casp1 in Lewy bodies of PD patients), plus the Catalytic cleft note that the P1 position of natural caspase-1 substrates have 100 % stringently conserved amino acid Asp (which we have identified as Asp121 in aSyn), the cleavage efficiency is determined by the surrounding residues (P10-P10'). divergent from the sequence YVHD found to be cleaved in caspase-1's natural substrate pro-IL-1b. (md). The broader inflammation-cluster narrative lives in inflammation; this page does not re-narrate NLRP3 / Pyroptosis / CAPS / Complement biology.

ShareFolder Mitochondria — asyn and mitochondria > Evidence in sPD

The mitochondria-bridge page on this topic is ShareFolder > Mitochondria > Astrocyte > asyn and mitochondria > Evidence in sPD (md). The page records Tsukada 2019 #903 brain energy metabolism (neurons OXPHOS / astrocytes glycolysis; Lopez-Fabuel 2016 #906 supercomplex / free Complex I contrast); the asyn and mitochondria table — Devi 2008 #1382 N-terminal 32 amino-acid cryptic mitochondrial targeting signal, Guardia-Laguarta 2014 #1383 wild-type α-syn in MAM rather than mito, Vicario 2018 #1384 review of mitochondrial respiration / Complex I / proteostasis / cytochrome c / calcium / membrane potential / ATP production effects of α-syn, Krzystek 2021 #1662 full-length vs 1-120-truncated aSyn mitochondrial-fragmentation contrast; the Evidence in sPD > Postmortem table — Schapira 1990 #877 SN ↓ MC1 activity, Gatt 2016 #1387 PD / PDD frontal-cortex MC1 activity / mtDNA / porin / TFAM / NDUFB8, Garcia-Esparcia 2018 #1388 MC1–5 mRNA fingerprints across iPD / PD / PDD frontal cortex and angular gyrus, Grünewald 2016 #935 single-SN-neuron LCM with mitochondrial mass, TFAM, TFB2M, mtDNA heteroplasmy, Keeney 2006 #944 frontal-cortex ND6 / NDUFA13 protein-carbonyl panel; and the CTL / PD MC1 mass mini- table at 39 / 30 / 20 / 15 / 8 kDa. The broader mitochondrial-cluster narrative lives in mitochondria (TRAP1, asyn-and-mitochondria sibling pages, mitophagy in vivo, MIBG); this page does not re-narrate that material.

ATP13A2 (Park9) — Lysosomal aSyn Entry

Pipeline of GD & GBA-PD > Supplement > ATP13A2 (Park9) > BBB / disruption / opener > BD > Process / BeyondBio > Biobank is the ATP13A2 / Park9 entry under the aSyn supplement chain (md). The Lewy-pathology Kalia and Kalia table also records ATP13A2 as + for protein-in-LB and − for LB-associated-with-disease (md).

GBA-PD ↔ aSyn Link

The GBA-PD pilot synthesis (gba-pd, gba-therapeutics) and per-compound entity pages (PR001, Ambroxol, Venglustat, Eliglustat) carry the GBA-PD α-synuclein readouts (Insoluble α-synuclein in 4L/PS-NA, Proteinase K-resistant aSyn, phospho-α-synuclein CSF, CSF total aSyn per-compound rows; pS129-aSyn PFF readouts). Tier 1 on this page contributes the a-syn POSTMORTEM matrix (md) which seats the Mazzulli / Murphy / Choi GBA-PD postmortem α-syn fractionation evidence; everything else in the GBA-PD pilot range is delegated to the pilot pages by Tier 2 designation in the boundary map (20240722_181748 through _181813, _182303, _182310, _182313, the Summary > 총정리 GBA protein & activity band _182123 → _182153, etc.).

Parkin / PARKN GT ↔ aSyn Link

parkin and PARKN GT own the Parkin protein / Parkin PD / PARKN GT (PFR-4249-100) / PINK-1 narrative, including the α-Syn PFF preclinical-model rows inside PARKN GT and the Parkin substrate-list synphilin-1 / aSyn (?) notes. The boundary map flags a meaningful scope contradiction: “the PARKN GT decision matrix uses α-syn pathology absence as a patient-selection criterion … ‘aSyn-related biomarkers are not planned for this project because aSyn pathology is rarely observed in the target population’” — read this against the Lewy-pathology table’s record of Parkin as + for protein-in-LB and +/- for LB-associated-with-disease (md).

Inflammation, Mitochondria, Biomarkers-Outcomes, PET / Imaging Links

  • inflammation — aSyn splicing / Pyroptosis / NLRP3 / CAPS / C5aR1 / Stratification cross-references; In Vivo strategy Katy uses α-synuclein PFF as the seeding model (20240722_183234, _183238, _183241).
  • mitochondria — TRAP1, asyn-and-mitochondria sibling rows, mitophagy in vivo, MIBG.
  • biomarkers-outcomes — CSF aSyn / RBD / SAA biomarker development, σ1R, NFL, retinal aSyn / Amydis, Synaptic biomarkers, Reference range, Outcome measures, RBD → PD / MSA / PDD-DLB conversion penetrance.
  • pet-imaging — aSyn PET / immunoPET / propagation-imaging cross-references.

Source Table

A single chronological table covering every Tier 1 source. This is the primary provenance ground-truth for the page. Numeric uncertain spans and embedded images are copied verbatim from each source note’s quality_metrics and match the boundary map.

stemnav path / headingsource notecanonicaluncertain spansembedded images
20240722_181818Pipeline of GD & GBA-PD > TAK-341 (MEDI1341) > PK/PD modelnotemd74
20240722_181822TAK-341 (MEDI1341) > Clinical studiesnotemd72
20240722_181827aSyn programs > aSyn Propagation Suppressornotemd70
20240722_181831SNCA BTV (HDO) (PFR-4067-100) > Executive summary (Ryouta Maeda)notemd101
20240722_181835SNCA ASO (WAVE) > Clinical plan of SNCA ASOnotemd72
20240722_182120α-Synuclein and Lewy pathology in Parkinson’s disease > Supplement Positive vs Negativenotemd40
20240722_182149Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activity > a-syn POSTMORTEMnotemd40
20240722_182451Pipeline of GD & GBA-PD > Supplement > PET for astrocyte > aSyn > Animal models of aSyn > Non-Spreading Modelsnotemd10
20240722_182454Pipeline of GD & GBA-PD > Supplement > aSyn > Animal models of aSyn > Non-Spreading Models > Spreading Modelsnotemd10
20240722_182457Pipeline of GD & GBA-PD > Supplement > aSyn > Animal models of aSyn > Spreading Modelsnotemd00
20240722_182501Pipeline of GD & GBA-PD > Supplement > aSyn > Animal models of aSyn > Non-Spreading Models > Spreading Modelsnotemd00
20240722_182504Pipeline of GD & GBA-PD > Supplement > Non-Spreading Models > Spreading Models > Summary of a-syn animal models > MOA of aSyn spreadingnotemd00
20240722_182507Pipeline of GD & GBA-PD > Supplement > Summary of a-syn animal models > MOA of aSyn spreading > Antibodies to aSyn > Astrocytic aSynnotemd00
20240722_182510Pipeline of GD & GBA-PD > Supplement > MOA of aSyn spreading > Antibodies to aSyn > Astrocytic aSyn > CSF & Blood (a-syn)notemd10
20240722_182514Pipeline of GD & GBA-PD > Supplement > Astrocytic aSyn > CSF & Blood (a-syn) > Distribution > Expression of aSynnotemd20
20240722_182518Pipeline of GD & GBA-PD > Supplement > Function (of normal aSyn) > Grading/Scoring of LB pathology > Homology > In vitro studies of aSynnotemd00
20240722_182522Pipeline of GD & GBA-PD > Supplement > Mutations SNCA > Neurodegeneration and aS… > Oligodendrocytic aSyn > PET aSynnotemd10
20240722_182524Pipeline of GD & GBA-PD > Supplement > Mutations SNCA > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSynnotemd00
20240722_182528Pipeline of GD & GBA-PD > Supplement > Mutations SNCA > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSynnotemd00
20240722_182532Pipeline of GD & GBA-PD > Supplement > Mutations SNCA > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSynnotemd00
20240722_182535Pipeline of GD & GBA-PD > Supplement > Mutations SNCA > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSynnotemd00
20240722_182539Pipeline of GD & GBA-PD > Supplement > Neurodegeneration and aSyn > Oligodendrocytic aSyn > PET aSyn > Postmortem aSynnotemd10
20240722_182542Pipeline of GD & GBA-PD > Supplement > Postmortem aSyn > Release > Safety for aSyn > KO of α-syn > Seed-Amplification Assaynotemd00
20240722_182545Pipeline of GD & GBA-PD > Supplement > Safety for aSyn > KO of α-syn > Seed-Amplification Assay > Quantificationnotemd00
20240722_182549Pipeline of GD & GBA-PD > Supplement > Seed-Amplification Assay > Quantification > Utility > Sources of aSynnotemd00
20240722_182552Pipeline of GD & GBA-PD > Supplement > Sources of aSyn > Skin aSyn > Species > Native conformation > Summary aSyn speciesnotemd10
20240722_182556Pipeline of GD & GBA-PD > Supplement > Summary aSyn species > NDE > Fragments (Truncation) > Assay Truncationnotemd00
20240722_182559Pipeline of GD & GBA-PD > Supplement > Summary aSyn species > NDE > Fragments (Truncation) > Assay Truncationnotemd00
20240722_182602Pipeline of GD & GBA-PD > Supplement > NDE > Fragments (Truncation) > Assay Truncation > Structure of aSynnotemd00
20240722_182606Pipeline of GD & GBA-PD > Supplement > Assay Truncation > Structure of aSyn > Synapse and aSyn > TM for aSyn programsnotemd00
20240722_182609Pipeline of GD & GBA-PD > Supplement > Synapse and aSyn > TM for aSyn programs > Turnover of aSyn > ATP13A2 (Park9)notemd00
20240722_182613Pipeline of GD & GBA-PD > Supplement > ATP13A2 (Park9) > BBB / disruption / opener > BD > Process / BeyondBio > Biobanknotemd00
20240722_183050Pipeline of GD & GBA-PD > Supplement > Other Biobanks > Biobanks in Japan > BIOMARKER > BioOrchestra > Inflammation > ALS > aSyn (therapeutic) antibody > Comorbiditynotemd50
20240722_183135Inflammation > NLRP3 > Neuronal > Caspase 1 > aSyn splicing > Catalytic cleftnotemd30
20240722_183436ShareFolder > Mitochondria > Astrocyte > asyn and mitochondria > Evidence in sPDnotemd40
20240722_184156MSA > aSyn in MSA > CSF aSyn in MSAnotemd40
20240722_184324PDE > PIAS2 > Pipeline of PD > aSyn - Antibodynotemd40
20240722_184327Pipeline of PD > aSyn - Antibody > aSyn - Small moleculesnotemd40
20240722_184330Pipeline of PD > aSyn - Vaccinenotemd13

Totals across these 39 Tier 1 sources: uncertain_span_count = 79, embedded_image_count = 12. Numbers match the boundary map.

Compact Tier 2 / Tier 3 Source Index

This page does not re-narrate Tier 2 / Tier 3 sources. The full inventory and per-stem provenance is on alpha-synuclein-source-boundary, under ## Tier 2 — α-Synuclein As Linking Axis Inside Another Topic (145) and ## Tier 3 — Passing Mention; Source-Table Row Only (54). Section roll-up at a glance:

sectionT2T3totalowner
gba-pd-asyn691988gba-pd, gba-therapeutics, PR001, Ambroxol, Venglustat, Eliglustat
inflammation24024inflammation
biomarkers-outcomes15015biomarkers-outcomes
parkin14014parkin, PARKN GT
msa909msa, msa, pipeline-msa
operations178operations
samples-collaborations178samples-collaborations
pet-imaging606pet-imaging
other-mechanisms044other-mechanisms
genetics-pathway044genetics-pathway
lysosome-autophagy044lysosome-autophagy
clinical-pd224clinical-pd
lrrk2033lrrk2
mitochondria303mitochondria
molecular-biology033molecular-biology
pk-gt-pharmacology112pk-gt-pharmacology
Tier 2 / Tier 3 totals14554199

Cross-topic totals across the boundary map: 39 + 145 + 54 = 238 candidate sources.

Uncertainties Carried Forward

These are review-priority hot spots. The boundary map’s Risk and Uncertainty Notes ranks the 15 highest-uncertainty pages across all 238 candidates; only the Tier 1 entries are listed here.

  • 20240722_181831 (T1, gba-pd-asyn) — uncertain_span_count = 10. SNCA BTV (HDO) Executive summary (Ryouta Maeda) cells include aSn / m RNA / b/c / NHP biodistribution befoe CN text-form artefacts; the long Ryouta Maeda 2022-07-13 paragraph has high-risk drug/program names (Ionis IT SNCA ASO, BIIB101), the SharePoint URL has SCNA vs SNCA ambiguity, and the HDO PET workflow flow- chart bottom is clipped near the lower edge.
  • 20240722_181818 (T1, gba-pd-asyn) — uncertain_span_count = 7, embedded_image_count = 4. TAK-341 PK/PD model: KD exponents, affinity-table rows, clone IDs (Aslo0543, asyn0087, Aslo0452), Figure 18 dose legend, and Cohort 2 / Cohort 3 visibility flags are flagged — re-check the canonical page.
  • 20240722_181822 (T1, gba-pd-asyn) — uncertain_span_count = 7. TAK-341 / MEDI1341 clinical-studies row labels, MAD dose values Cohort 2 (2400 mg) / Cohort 3 (4800 mg), MSA study FPI in 202207 shorthand. The TAK-341 POM mini-table dose rows / percent-change values are preserved as figure evidence with only obvious fragments transcribed.
  • 20240722_181827 (T1, gba-pd-asyn) — uncertain_span_count = 7. The SNCA BTV TfR construct (PaddleOCR TfR vs Apple TTR) and Cumulative Cost 5 oku¥ / 3 oku¥ overlap, plus the αS mAb Roche/prothema (vs Prothena) cell.
  • 20240722_181835 (T1, gba-pd-asyn) — uncertain_span_count = 7. SNCA ASO PK/PD Imax placement under WV columns, projected-KD footnote, the a(and biomarker calibration?)? a Key go/no-go criteria? shorthand.
  • 20240722_183050 (T1, gba-pd-asyn) — uncertain_span_count = 5. BioOrchestra aSyn (therapeutic) antibody > Comorbidity page: 82,452 controls value, 67.0 % of women gender-column attribution, Acquadro spelling, 7x vs HC IL-1b of HBP (d=1.38) Cohen’s d.
  • 20240722_182149 (T1, gba-pd-asyn) — uncertain_span_count = 4. Choi 2011 SDS-soluble absent/present cell-position alignment; FRACTIONATION leftmost labels (Korean clip); 8 % SDS & 8 M urea; bottom Sidransky-table fragment.
  • 20240722_182120 (T1, gba-pd-asyn) — uncertain_span_count = 4. Lewy-pathology continuation paragraph begins mid-sentence with o parkinsonism,; postmortem matrix column-row alignment for the duplicated Brain / CSF rows.
  • 20240722_184156 (T1, gba-pd-asyn) — uncertain_span_count = 4. MSA CSF aSyn in MSA left-edge clipped citation prefixes ({Ateno, 2012 #1467}, {ga, 2018 #1623}, {ulds, 2012 #2455}) and Yazawa 2005 {...original' stray apostrophe.
  • 20240722_183436 (T1, gba-pd-asyn) — uncertain_span_count = 4. ShareFolder asyn and mitochondria > Evidence in sPD: Korean fragment about Mt-impairment chronic neuroinflammation, Lopez-Fabuel row text clipped by embedded thumbnail, Schapira parenthetical imbalance, Keeney 8 kDa subunit (NDUFA13) numeral ambiguity.
  • 20240722_184324 (T1, gba-pd-asyn) — uncertain_span_count = 4. Pipeline of PD aSyn - Antibody Target / mechanism / Design / results table cell boundaries flagged not 100 % confirmed; Nitrase result-cell first letters clipped (ntroduction, itrase's, modification).
  • 20240722_184327 (T1, gba-pd-asyn) — uncertain_span_count = 4. Pasadena trial-design footnote glyph; ABL301’ apostrophe; 200-11, 30599 (313), zasolmin /norvatis token-list (likely minzasolmin (UCB0599) developed with Novartis but visible source text reads as transcribed).
  • 20240722_184330 (T1, gba-pd-asyn) — uncertain_span_count = 1, embedded_image_count = 3. Prior-table row source/phase/status alignment partly cut by crop position; AFF008 study series figure and CSF Oligo-aSyn boxplots are body-embedded figure assets.
  • PARKN GT decision-matrix scope contradiction (cross-page) — the topics/parkin synthesis records the PARKN GT (PFR-4249-100) decision matrix as omitting aSyn-related biomarkers because aSyn pathology is rarely observed in the target population, while the Lewy-pathology Kalia and Kalia table records Parkin as + for protein-in-LB and +/- for LB-associated-with-disease (md). Re-check before any downstream use.
  • CSF Oligomeric vs total aSyn fold ratio (20240722_182514, T1) — the page’s Js summary records Oligomeric a-syn level is much greater than total a-syn (about ?-fold) with the ? placeholder preserved verbatim (uncertain_span_count = 1 covers this). Do not resolve the placeholder from secondary sources.
  • GBA-PD Summary > 총정리 GBA protein & activity band overlap risk — boundary map flags risk of double-narration if Tier 2 pages in this band are re-narrated here. They are not; the GBA-PD pilot synthesis owns them.
  • Brain Bank / BioOrchestra cluster promotion candidate — 20240722_182722 (Tier 2 in the current boundary map, propagation / Braak / Masuda-Suzukake α-syn fibrils content) is flagged in the boundary map as a candidate for promotion to Tier 1 if the body is re-checked. Not narrated on this page in the current pass.

그래프 뷰

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