Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies

Koss, David J.; Erskine, Daniel; Porter, Andrew; Palmoski, Pawel; Menon, Hariharan; Todd, Olivia G. J.; Leite, Marta; Attems, Johannes; Outeiro, Tiago F.

doi:10.1186/s40478-022-01403-x

Acta Neuropathologica Communications

Table 1 Human tissue cohort

From: Nuclear alpha-synuclein is present in the human brain and is modified in dementia with Lewy bodies

Disease	n	Sex (% male)	Age (years)	PMI (hrs)	NFT Braak stage	Thal Phase	CERAD	NIA-AA	LB Braak stage	McKeith Criteria
Histology-qualitative
Con	6	66.70%	60–90	24–85	0-IV	0–3	neg-B	Low-inter	0	100%-No LB
			82 ± 4.5	55.3 ± 9.5	16.6%-0	16.6%-0	83.3%-neg	83.3%- low	100%-0
					16.6%-I	16.6.%-1	16.6%-B	16.6%-inter
					33.3%%- II	16.6%-2
					16.6%-III	50%-3
					16.6%-IV
DLB	9	66.70%	72–91	10–99	I–III	0–4	*neg-B	Not-inter	*6	100%-Neo
			78.2 ± 1.9	55 ± 12.1	11.1%-I	14.3%-0	55.6%-neg	11.1%-not	100%-6
					89.9%-III	14.3%-1	22.2%-A	55.6%-low
						14.3%-2	22.2%-B	33.3%- inter
						14.3%-3
						42.9%-4
Histology – pS129 nuclear quantification
Con	12	58.30%	60–95	15–66	0-III	0–5	neg-A	Not-inter	0	100%-No LB
			81 ± 3.2	42 ± 5.4	25%-0	41.7%-0	91.7%-neg	41.7%-not	100%-0
					50%-II	25%-1	8.3%-A	50%-low
					25%-III	8.3%-2		8.3%-inter
						8.3%-3
						8.3%-4
						8.3%-5
DLB	12	91.60%	71–91	8–98	II–III	*0–5	neg-B	Not-inter	*4–6	16.7%-limbic
			78.5 ± 1.7	38.8 ± 8.8	41.7%-II	30%-0	60%-neg	20%-not	12.5%-4	83.3%-Neo
					58.3%-III	10%-1	10%-A	30%-low	87.5%-6
						10%-2	30%-B	50%-inter
						20%-3
						10%-4
						20%-5
Western blot
Con	9	55.60%	73–99	5–75	0-III	0–4	neg	Not-low	0	100%-No LB
			85.3 ± 2.7	31.7 ± 7.4	22.2%-0	22.2%-0	100%-neg	22.2%-not	100%-0
					11.1%-I	22.2%-1		77.7%-low
					55.6%-II	11.1%-2
					11.1%-III	33.3%-3
						11.1%-4
DLB	8	75%	68–92	8–99	II–III	03-May	neg-B	Low-inter	05-Jun	100%-Neo
			78.5 ± 3	39.5 ± 11.9	37.5%-II	12.5%-3	62.5%-neg	87.5%-low	25%-5
					62.5%-III	62.5%-4	25%-A	12.5%- inter	75%–6
						25%-5	12.5%-B
Mass spectrometry
Con	3	33.30%	64–99	5–93	I–II	0–1	neg	Not-low	0	100%-No LB
			81 ± 10.1	41 ± 26	33.3%-I	66.7%-0	100%-neg	66.7%-low	100%-0
					66.7%-II	33.3%-1		33.3%-inter
DLB	3	100%	78–81	8–34	III	03-Apr	A-B	Low-inter	6	100%-Neo
			79.7 ± 0.9	22.7 ± 7.7	100%-III	33.3%-3	33.3%-A	33.3%-low	100%-6
						67.7%-4	67.7%-B	66.7%-inter

Human cases use for histology, western blot and mass spectrometry. Case are separated by disease classification according to non-diseased controls (Con) and dementia with Lewy bodies (DLB). Case numbers (n), sex, age, post-mortem interval (PMI), neurofibrillary tangle (NFT) Braak stage, Thal phase, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the National Institute of Ageing—Alzheimer’s Association (NIA-AA) criteria, Lewy body (LB) Braak stage and McKeith criteria are provided. For age and PMI both range and mean ± SEM are provided. For numerical scores of pathology, range and percentage composition are given. For CERAD scores, negative (neg), A and B reported. For NIA-AA, not, low and intermediate (inter) risk for Alzheimer’s disease. For McKeith criteria, only percentage composition is given, where cases free of LBs (No LB) and neocortical predominate (Neo) are indicated. * = based on available data

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