20240722_184600

Resource: Mizushima 2020

Urine

	cohort	Overlap with CSF proteins
{Karayel 2021 #2257w}	HBS and LCC	- 63% of CSF-abundant proteins (1728) overlaps with urine-abundant proteins (2365) - 46% of urine-abundant proteins (2365) overlaps with CSF-abundant proteins (1728) - 36% (1080) of all identified proteins in both biofluids - 이 overlapping protein 들은 pearson r=0.49 - The most abundant proteins present in both included ALB, PTGDS, ORM1, SERPINA1, B2M and several apolipoproteins and immunoglobulins

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Yan

	GBA activator	GBA GT	Parkin GT	cGAS
20201110	- PE : Feb 2021 - Retinal - * histology - PLR: budget	Cognition , natural Hx study	- MC1: Tsujihata san , fibroblast availability, readout, - Other mito bm: mitochondrial isolation	- Cgamp prototype established.
	TPP	GBA PET
		TCP
		aSyn PET
		Lysosomal MBMs
		aSyn MBM (Oligomer)
20210422	MSA	김한준, SNCA ASO, MAIko, animal model,
	Jaya	MDS-UPDRS
	MC1	Ashley
	MT stratification	Kamiguchi, Daria
202105	Snca hdo	Timeline, biodistribution discussion using ionis data (cole, putamen has the lowest KD efficacy)
	Mc1	Fibroblast ordering, CRO (TNT):cost, can I use fy21 NSTM-Shonan budget for this?
	sample	Parkinson's UK brain bank
20210520	MSA	ePOC definition, natural Hx studiy
	mt	AMED
	TAK341	Simuni
20210527	MSA	, natural Hx studiy
	mt	AMED
		Firoblast study: Order, ERC,
		Parkin-PD epidemiology in AMP-AD
20210610	MC1	Order, protocol, flow (homogenate → intact cells?)
		NBB
		31p MRS
		Parkin PET
		BD support: NZP, Progenra, LTI (LYso Tx)
20210610	biobank	NBB, GE
		NZP, 31P MRS
	MSA	KAUFman,
		Toshiya,
	mito	Arthur
20210713	biobank	NBB, GE
	BD	NZP,
	Mito	31P MRS
		Parkin PET
20210720		31p MRS
		GE
		NBB
		Lysosomal , Comp Bio

{Higginbotham, 2020 #1497}

CSF DES: there were a total of 225 proteins with significantly decreased abundance and 303 proteins with significantly increased abundance in AD. The
Brain proteomics: 165 highly altered proteins → 44 modules and cell type changes
[Overlap analysis] Overlap between brain protein and RNA networks: reveals shared and protein-specific module changes
the majority of the 44 modules in our discovery brain proteome network did not significantly overlap in transcriptome network. Even among those 34 protein modules highly preserved across our discovery and replication brain proteomes, only 14 (~40%) demonstrated statistically significant overlap with the transcriptome by Fisher's exact test (FET) (Fig. 3A). Several protein modules associated with
→ 15 modules
integrative analysis: CSF and brain proteomes → 14 brain modules with statistically significant overlap in the discovery CSF dataset,
4-1 meaningful overlap among (i) CSF proteins significantly increased in AD and (ii) CSF proteins significantly decreased in AD → 8 of the 44 brain modules significantly overlapped with proteins increased in AD CSF (M12, M1, M2, M18, M5, M44, M33, and M38), while only two modules (M6 and M15) demonstrated meaningful overlap with proteins decreased in AD CSF.
CSF replication → 60 validated brain-linked CSF targets (근데 이 60개가 consistency between brain & CSF, between RNA & Protein을 보이는 최종산물이 아니라네?) 결국은 you have to see fig S5.

Figure S5 panels

Brain-CSF integrative analysis | 271 brain-linked CSF targets of interest | CSF replication 1 | 60 validated brain-linked CSF targets

Panel	Module label	Genes
Synaptic panel	M12 / M1	AP2B1, BASP1, DTD1, GAP43, GDA, NK1, NPRT1, LDHA, YWHAB, YWHAZ
Vascular panel	M16 / M6	ACBP1, AHSG, AMBP, C5, COL14A1, COL18A1, CP, DCN, F2, KNG1, LAMA5, LUM, MFGE8, NID2, NUCB2, OGN, OLFML3, PON1, VTN
Myelination panel	M2 / M4	DDAH1, GD11, GSS, GSTO1, PEBP1, PPIA, PTPRZ1, SOD1, SPP1
Glial Immunity panel	M18 / M5	ALDOC, ENO1, GLO1, GLO3A, GMFB, MARCKS, PARK7, SMOC1, SPON1
Metabolic panel	M3 / M33 / M38	ALDOA, CALM3, ENO2, GOT1, GOT2, GPI, KRT2, MDH1, PGAM1, PGK1, PNM, TPI1, YWHAG

Figure S5. Brain-linked CSF biomarker panels demonstrate divergent expression brain and CSF. A-E) Protein expression trends of the overlapping modules comprising the marker panels. Module (M) eigenproteins depict expression profiles in the brain proteome, while volcano plots demonstrate the differential expression (log₂ AD vs CT) of proteins in the CSF discovery proteome. ANOVA with Tukey post-hoc correction was used to assess the statistical significance of module eigenprotein abundance changes across the four groups of the brain discovery cohort. Abbreviations: CT, Control; PD, Parkinson’s Disease; AD, Alzheimer’s Disease.

In each panel:

Brain Eigenprotein boxplots compare CT / PD / ADPD / AD groups (showing p-values like p = 0.044, p = 0.00048, p = 0.27, p = 0.49, p = 0.000058, p = 0.29, p = 9.4E-07, p = 5.8E-08, p = 0.0017, p = 0.29, p = 0.0088).
CSF -Log₁₀ p-Value volcano plots show genes labeled along Up / Down axes (Log₂ AD vs CT).
AD Expression Trends footers show Brain ↑/↓ CSF ↑/↓ pairings per panel.
The Immune Response sub-panel of M5 highlights PARK7.

Voyager

(…) ct Bon (Voyager). Following up on interest on novel systemic delivery brain targeted capsids. Note, Declined interest in Vectorized antibodies as alternative approach to target intracellular proteins. Revisit Targets available:

i. Parkin. Available i. XTM1. Available ii. DMD. Available iv. GBA. Voyager has program but could consider. Comes down to strategy, timing, and $. Open to discussions but have another party who has expressed interest v. HTT. Voyager has program but could consider. Comes down to strategy, timing, and $. vi. SOD1 for ALS. Voyager has program but could consider. Comes down to strategy, timing, and $

Uncertain Spans

Yan section 첫 행 “20201110 / GBA activator: PE : Feb 2021 / Retinal / * histology / PLR: budget” 의 별표(*)는 typography 상 작은 점인지 별표인지 모호함. 별표로 옮김.
“Karayel 2021 2257w” 의 끝 글자 ‘w’ 는 OCR/사진 모두 모호하나 가장 잘 보이는 형태로 옮김. (#2257 + 알파벳 suffix 인지 단독 #2257 인지 확정 어려움)
Figure S5 패널 안의 gene-symbol 라벨 (예: Synaptic 패널 M12 boxplot 옆 OKB8, NO0LBu, CDV3, KPT2 같은 개별 dot label)은 너무 작아 본문에 옮기지 않고 evidence crop 만 보존. 표에 정리한 gene 목록은 panel-level의 큰 라벨 텍스트만 포함함.
“Voyager” 섹션 첫 줄의 좌측이 잘려 시작함 (“ct Bon (Voyager)…”). 잘린 앞부분 텍스트는 본 페이지에서 판독 불가능.

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