CSF & Blood (a-syn) study rows continued (Schirinzi 2019 / Wang 2012 / PD01A / Lin 2019 / Chang 2019 / Wang 2020 / Chatterjee 2020 / Yamashita 2023 / Transpharmation Attyloid Blömeke 2022), Js summary table, MDS 2020 PD01A note, Distribution, Expression of aSyn, Bulk tissue SNCA violin plot, Postmortem brain study rows
CSF & Blood (a-syn) — study rows continued
| citation | cohort | sample | findings | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (Schirinzi, 2019 #615) | Tor Vergata Univ Hospital (Italy) | CSF | 46 PD patients, 원문 확인하니, CSF total 도 ↓ (ie ↓ 33% p<0.05, ELISA kits (Covance)) | |||||||||||||||
| (Wang, 2012 #1261) | Oregon Health and Science Uni, uni of washinton, USCS etc (Dis duration 정보 X) | CSF |
- Discovery set & validation set 모두 elevated in PD by 10-30% (눈대중) - Oligomeric aSyn : NA - MSA에선 오히려 감소 - PS-129 CSF concentrations correlated | |||||||||||||||
| PD01A (ACI-7104) | P1 in PD | CSF | (Volc, 2020 #932) Majbour's Syn-O2 antibody, fig (motor) scores was r=0.515 | |||||||||||||||
| (Lin, 2019 #1255) | 122 PD patients, 68 controls, Taiwan | Plasma, clinical SX만, Longitudinal |
- plasma levels of total and pS129-α-syn 36.6 fg/mL, p < 0.001; pS129-α-syn: 1.1% vs. 1.1 _ 0.6%, p = 0.01). - Among PD patients, pS129-α-syn levels III scores (r = 0.27, 95% CI: 0.09-0.4..) - However, we found no remarkable c - After a meanfollow-up of 3.5 _ 2.1 years, PD patients with baseline pS129-α-syn levels above the threshold (≥ 8.7 fg/mL) were ~3.0 lag, taller progression of at least 3 points in the III | |||||||||||||||
| (Chang, 2019 #2739) | 40 PD, 48 HC, Taiwan | Plasma & serum | Compared with the HCs, both plasma and serum α-synuclein levels were significantly higher in the PDs (P < 0.001 and P < 0.001 respectively). | |||||||||||||||
| (Wang, 2020 #1638) | 40 PD, 40 HC, China | plasma | A o-α-synuclein concentration bar plot for Control group vs PD group | |||||||||||||||
| (Chatterjee, 2020 #1263) | 27 PD, 15 HC, India | serum |
- Normal: ~22, H&y 1: ~10, H&y 2&3: ↓ - Fig. 1C, showed that total α-synuclein level was not significantly different in PD (23.13 ± 1.88 ng/ml) compared to controls (24.87 ± 6.69 ng/ml) (p=.608). There was no significant difference in phosphorylated α-synuclein level between PD (17.51 ± 2.36 ng/ml) and controls (23.15 ± 4.69 ng/ml) (p=) | |||||||||||||||
| (Yamashita, 2023 #2740) review | review | review | As the recent systematic review by Paul Lingor's group notes, recent research has focused on specific forms of alpha-synuclein, because unfortunately data on total alpha-synuclein serum levels has been historically contradictory (T inges et al., 2022). | |||||||||||||||
| Transpharmation Attyloid | (Blömeke, 2022 #2639) German | CSF |
- sFIDA (surface-based fluorescence intensity distribution analysis), (specificity of 73%, and a sensitivity of 64% with an AUC of 0.88 - capture antibody, using the same epitope for capture and decision, only oligomers are probed, not monomers, is measured (single oligomers are detected and counted by fluorescence microscopy) - characterization: size 를 봤다 (no further duration) - Question: correlation with MDS-UPDRS? → no difference Long sample Will be assessed in future.
|
Js: in CSF PD, Oligomeric a-syn level is much more greater than total a-syn (about ?-fold) difference of detection methods.
Summary
| ↑ vs HC (Baseline) | Longi change | Correlation with UPDRS | ||
|---|---|---|---|---|
| p-aSyn | CSF | 1.2X | NA | NA |
| Blood | 16X (No overlap) | NA | Weak correlation (r=0.27) | |
| NFL | CSF | 1.25x | stable | |
| Blood | 1.4x, 1.6x, 1.1x | Slight increase | modest correlation (r=0.42) |
MDS 2020, Oral presentation of PD01A: CSF Total aSyn is mainly composed of monomeric aSyn (Mollenhauer et al. 2017, PMID 28734051) CSF aSyn predominantly derives from neurons in from the peripheral blood. 80% of CSF composition (ie, proteins) derives from the filtration of peripheral blood, whereas 20% derives from CNS cells.
Distribution
- abundant in the nervous system under normal conditions
- predominantly expressed in neurons and preferentially localized to presynaptic terminals and possibly the nucleus
- Normally in both soluble and membrane-associated fractions (Suzuki, 2020 #1029)
- α-syn mainly localizes in glutamatergic terminals (Taguchi et al., 2016).
| Young | Terminal 위주 (soma 에는 조금) (Chu and Kordower, 2007) |
| elderly | Concentrate in soma (Chu and Kordower, 2007) |
Expression of aSyn
mally:
-
predominantly expressed in neurons
-
astrocyte don’t express aSyn
-
RBCs have massive amount of aSyn,
-
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.
Bulk tissue gene expression for SNCA (ENSG00000145335.15)
Violin plot. Categories visible across the x-axis (left → right):
- Brain - Amygdala
- Brain - Anterior cingulate cortex (BA24)
- Brain - Caudate (basal ganglia)
- Brain - Cerebellar Hemisphere
- Brain - Cerebellum
- Brain - Cortex
- Brain - Frontal Cortex (BA9)
- Brain - Hippocampus
- Brain - Hypothalamus
- Brain - Nucleus accumbens (basal ganglia)
- Brain - Putamen (basal ganglia)
- Brain - Spinal cord (cervical c-1)
- Brain - Substantia nigra
IB) Human α-syn basal levels in plasma: 0.9 nM
α-syn basal levels in brain: 0.093 nM
Postmortem brain α-syn study rows
| citation | tissue | findings |
|---|---|---|
| (Falek et al. PMID 5004) | Postmortem, brain |
• extracted from mid-brain tissue, including the substantia nigra of PD brains, overall the SNCA mRNA levels were increased in PD brains an average of nearly fourfold over normal control mid-brain, although there was much greater variability in samples from PD patients compared to controls. • Frontal cortex samples from selected individuals were also analyzed. SNCA mRNA levels were not significantly changed in PD frontal cortex compared to controls. |
| (et al. 2005, PMID 15719423) | leukocytes | -syn gene mRNA expression in sporadic PD did not differ from healthy controls (median [range] 0.110 [0.012-0.628] vs. 0.120 [0.028-0.447]; P 0.15). There was no difference in the -syn gene mRNA expression |
| (sbury et al. PMID 671) | Postmortem, brain | mRNA expression was reduced significantly in melanized substantia nigra neurons and frontal cortex neurons in Parkinson's disease |
| (tat et al. 1999, PMID 10348463) | Ipha-syn mRNA was significantly diminished in the substantia nigra of patients with PD compared with control subjects, but not in the cortex. |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Lin 2019 row | pS129-α-syn: 1.1% vs. 1.1 _ 0.6%, p = 0.01). | reads as written; the underscore as ± placeholder is preserved verbatim. |
| Js summary | about ?-fold | reads as written; the ? placeholder is preserved verbatim. |