| Dark | Bright | Bright | |
|---|---|---|---|
| Inflammation (infection, demyelination) | T1-weighted (axial brain MRI) | T2-weighted (axial brain MRI) | Flair (axial brain MRI) |
| very sensitive to pathology and makes the differentiation between CSF and an abnormality much easier. | |||
MRI in PD
| {Booth, 2015 #1745} REVIEW |
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MRS in PD
| {Booth, 2015 #1745} REVIEW |
|
MSA
Good review: {Stefanova, 2023 #2300}
Animal models of MSA
| promoter | |||
|---|---|---|---|
| (PLP)-hα-syn transgenic mouse ('Poewe MSA mouse model') | PLP (proteolipid protein) Promoter, (transgenic protein was detected in oligodendrocytes but in no other brain cell type.), =CSF aSyn level |
- FIG2A) Overexpresses human WT α-syn specifically in oligodendrocytes - (total) Asyn: ~6 fold increase in whole brain (ELISA) (vs WT) - FIG2B) soluble/insoluble, monomer/oligomer 모두 ↑ (Syn1, wb) , - GCI-like structures (oligodendrocyte에는 확실, 그러나 neuron, astrocyte, microglia에는 겨우 작은 human aSyn반 보이는 정도임) {Refolo, 2018 #1419} - GCI-like structures: with variable density and (wide-spread) distribution throughout the brain (Fig. 1f, striatum, SN, pontine nuclei, cbll cortex, inf olives 주:cerebral cortex는 안 감!) even at very early age (아마 2m부터?). at very early age. The GCI-load does not change with aging but caudal쪽이 더 심함. - (fig 8) 6m부터 (Soluble) oligomeric aSyn 생기며, ↑microglia, ↓DA, ↓motor function - the total level of (soluble & insoluble) monomeric aSyn is stable over time), - - Olivopontocerebellar motor loops remained spared (의미?), Cerebellar Purkinje 와 pontine cell loss는 x (GCI는 있는데?) - Demyelination is not typically found - Brain wt loss since 9m old (fig 3b), - ↓ neurons and oligodendrocytes in SC (FIG3) - GCI O, asyn accumulations in neuropil (f, axonal spheroids in cortex (indicating axonal degeneration, fig4e), gliosis o, insoluble aSyn accumulation, demyelination, - Remarkable gliosis in brain and spinal cord (fig 4g & h), axonal degeneration in cbll (GAP, fig4i, 24 m, cerebral WM) - GCI like inclusion & aSyn accumulation in oligodendrocytes and neuropil in (fig4b, 24 m, cerebral WM) - Axonal spheroids in cerebral cortex (24m, fig4e,f), - Degenerated myelin sheaths with degenerating axons in spinal cord (fig 6e) - Loss of myelinated axons in spinal cord (fig 6j) |
(MGI:3604008) TSHO does not have a license and did not used in the past research. {Heras-Garvin, 2020 #1121, 2nd} {Yazawa, 2005 #1440, original' |
| M2 mice, (CNP)-hα-syn transgenic mouse | 2',3'-Cyclic-nucleotide 3'-phosphodiesterase CNP promoter [81 model under the ]. |
overexpresses human α-syn in oligodendrocytes, - Fig1b: =total aSyn (SNL1, WB) ↓ ROTArod test, ↓ wire test (grip strength) | |
| viral-based animal models overexpressing α-syn in oligodendrocytes in rats and NHPs [77,79] | |||
| mouse model of adult-onset MSA based on the Cre-loxP system, which expresses inducible α-syn in oligodendrocytes [82]. | |||
| MBP-aSyn mouse | Ubhi K, Rockenstein E, Mante M, Inglis C, Adame A, Patrick C, Whitney K, Masliah E (2010) Neurodegeneration in a transgenic mouse model of MSA is associated with altered expression of oligodendroglial-derived neurotrophic factors. J Neurosci 30:6236-6246 | ||
| (f) Hasegawa 2016) | Mice injected with MSA brain homogenate develop neuronal a-syn pathology, but not in oligodendrocytes. |
aSyn in MSA
Brain aSyn in MSA
| {Schweighauser, 2020 #2060} seeding capacity: GCI-aSyn vs LB-aSyn | The cores of α-syn filaments extracted from the cerebellum of MSA patients or assembled from recombinant protein in vitro encompass around 70 amino acids, extending approximately from residues 30-100 (30). |
|
In vitro: GCI α-syn has been reported to be approximately three orders of magnitude more potent than Lewy body α-syn in seeding aggregation of α-syn (36). biologically distinct. 이의 원분 {Peng, 2018 #2062}: GCI-α-Syn forms more compact structures and is ~1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation | |
|
In vivo: {Prusiner, 2015 #2063} Inoculation of a-syn aggregates from MSA but not PD cases induced deposition of phosphorylated a-syn Solubility in SDS distinguishes a-syn filaments of MSA from those of DLB (44). |
CSF aSyn in MSA
| 평 | Js: 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} |
(boxplot of alpha-synuclein (pg/ml) 0-400 across Control n=11, AD n=9, DLB n=6, PD n=11, MSA n=12; significance brackets with * p<0.05, ** p<0.01, *** p<0.001). FIGURE 1. Alpha-synuclein concentration in the cerebrospinal fluid in degenerative neurological diseases. Statistical analysis was made by the Mann-Whitney U test. AD indicates Alzheimer disease; DLB, dementia with Lewy bodies; MSA, multiple system atrophy; PD, Parkinson disease. |
| {Mavroudis, 2020 #1468} anlysis | , CSF aSyn levels were significantly different in LBD compared with AD, but no statistical difference was found between PDD, MSA, PSP, and FTD. (HC와 비교는 안 함) |
| {ga, 2018 #1623} review | Total α-syn in CSF have been often examined, but with inconsistent results. Of nine studies using antemortem CSF, six revealed ↓ total α-syn in MSA patients vs control subjects, while three other studies did not show difference between the two groups (table 1). |
| {ulds, 2012 #2455} 76 | [Postmortem] ... |
Uncertain Spans
- “{Ateno, 2012 #1467}” — the citation surname is partially obscured at the left edge of the row; the leading character may be ‘I’ or ‘A’; rendered here as the OCR’s reading.
- “{ga, 2018 #1623}” and “{ulds, 2012 #2455}” — the citation prefixes are clipped at the left edge of the page, only the trailing characters are visible.
- “GCI O, asyn accumulations in neuropil (f,” — the trailing single character
f,is likely a section/figure tag truncated at the row boundary; the actual figure number is not unambiguously readable. - “{Yazawa, 2005 #1440, original’” — the source line ends with a stray apostrophe in the rendered cell; whether the closing brace is present is unclear from the visible crop.