The amyloid plaque proteome in early onset Alzheimer’s disease and Down syndrome

Drummond, Eleanor; Kavanagh, Tomas; Pires, Geoffrey; Marta-Ariza, Mitchell; Kanshin, Evgeny; Nayak, Shruti; Faustin, Arline; Berdah, Valentin; Ueberheide, Beatrix; Wisniewski, Thomas

doi:10.1186/s40478-022-01356-1

Acta Neuropathologica Communications

Table 2 48 proteins consistently enriched in plaques in EOAD and DS

From: The amyloid plaque proteome in early onset Alzheimer’s disease and Down syndrome

Uniprot	Gene	Protein	Enrichment in EOAD plaques (fold change)	Enrichment in DS plaques (fold change)	Known plaque protein?	Difference in AD brain tissue	Mediates Aβ pathology?
Previously confirmed plaque proteins—immunohistochemistry
Q9BXS0	COL25A1	Collagen alpha-1	104.3	113.1	Yes [74]	Increased	Increases pathology [6, 75]
O95631	NTN1	Netrin-1	34.9	58.7	Yes [60]	Increased	Decreases pathology [76]
P21741	MDK	Midkine	31.4	70.4	Yes [77]	Increased	Decreases pathology [78]
Q92743	HTRA1	Serine protease HTRA1	19.0	42.8	Yes [79]	Increased	Decreases pathology [80]
Q9H4F8	SMOC1	SPARC-related modular calcium-binding protein 1	12.9	58.8	Yes [60]	Increased	Unknown
P02649	APOE	Apolipoprotein E	10.4	17.2	Yes [81]	Increased	Increases pathology [82, 83]
Q14956	GPNMB	Transmembrane glycoprotein NMB	7.8	17.8	Yes (in plaque-associated microglia) [84]	Increased	Unknown
P0C0L4	C4A	Complement C4-A	7.5	10.1	Yes [85]	Increased	Unknown
P35052	GPC1	Glypican-1	7.5	8.5	Yes [86]	Decreased	Increases pathology [87]
P02743	APCS	Serum amyloid P-component	4.9	10.8	Yes [88]	Increased	Increases pathology [89]
Q9UIK5	TMEFF2	Tomoregulin-2	4.8	6.9	Yes [90]	N/a	Decreases pathology [91]
P02746	C1QB	Complement C1q subcomponent subunit B	3.3	4.3	Yes [92]	N/a	Increases pathology [93, 94]
P10909	CLU	Clusterin	3.2	4.0	Yes [95]	Increased	Increases pathology [7, 96]
Q00604	NDP	Norrin	2.9	4.6	Yes [79]	Increased	Unknown
P05067	APP	Amyloid-beta precursor protein	2.8	5.9	Yes [97]	Increased	Increases pathology [98]
P02747	C1QC	Complement C1q subcomponent subunit C	2.7	8.4	Yes [92]	Increased	Increases pathology [93, 94]
P01024	C3	Complement C3	2.5	2.9	Yes [92]	Increased	Increases pathology [94, 99, 100]
P41222	PTGDS	Prostaglandin-H2 D-isomerase	2.2	3.0	Yes [101]	Increased	Decreases pathology [101]
P26038	MSN	Moesin	2.1	2.6	Yes, in plaque-associated microglia [102]	Increased	Decreases pathology [103]
P07093	SERPINE2	Glia-derived nexin	2.1	4.3	Yes [104]	Decreased	Increases pathology [105, 106]
Q9UBP4	DKK3	Dickkopf-related protein 3	2.1	1.8	Yes [107]	Increased	Decreases pathology [108]
Q8IV08	PLD3	Phospholipase D3	2.0	2.0	Yes [109]	N/a	Decreases pathology [110, 111]
O00468	AGRN	Agrin	1.9	2.9	Yes [112]	Increased	Decreases pathology [113]
Q07954	LRP1	Prolow-density lipoprotein receptor-related protein 1	1.8	2.1	Yes [114]	Increased	Inconsistent effects on pathology [115]
P08670	VIM	Vimentin	1.7	1.8	Yes, in surrounding astrocytes [116]	Increased	Increases pathology [117]
P16870	CPE	Carboxypeptidase E	1.6	2.1	Yes [118]	Increased	Unknown
Q15818	NPTX1	Neuronal pentraxin-1	1.6	1.7	Yes [119]	Increased	Increases pathology [120]
Previously confirmed plaque protein—proteomics
Q9NRN5	OLFML3	Olfactomedin-like protein 3	19.2	18.9	Yes [44]	Increased	Unknown
Q9HCB6	SPON1	Spondin-1	6.9	16.5	Yes [44]	N/a	Decreases pathology [121, 122]
O94985	CLSTN1	Calsyntenin-1	5.4	8.1	Yes [44]	Decreased	Increases pathology [123]
Q9ULB1	NRXN1	Neurexin-1	2.9	2.8	Yes [44]	Increased	Unknown
P51797	CLCN6	Chloride transport protein 6	2.8	9.7	Yes [44]	Increased	Unknown
Q9NVJ2	ARL8B	ADP-ribosylation factor-like protein 8B	2.2	2.9	Yes [44]	Increased	Decreases pathology [124]
Novel plaque proteins—mechanistic link with Aβ or APP
O75110	ATP9A	Probable phospholipid-transporting ATPase IIA	1.8	2.3	No, but associated with Aß [125]	Increased	Increases pathology [125]
P15311	EZR	Ezrin	1.7	2.6	No, but associated with APP [103]	Increased	Decreases pathology [103]
O00299	CLIC1	Chloride intracellular channel protein 1	1.6	1.7	No, but associated with Aß [126]	Increased	Increases pathology [126]
O14773	TPP1	Tripeptidyl-peptidase 1	1.6	2.1	No, but associated with Aß [127]	Increased	Decreases pathology [127]
Novel plaque proteins—no previous association with Aβ or APP
P51809	VAMP7	Vesicle-associated membrane protein 7	3.0	4.0	No	N/a	Unknown
Q9UNK0	STX8	Syntaxin-8	3.2	2.4	No	Increased	Unknown
Q5TH69	ARFGEF3	Brefeldin A-inhibited guanine nucleotide-exchange protein 3	3.2	5.2	No	Increased	Unknown
Q6IAA8	LAMTOR1	Ragulator complex protein LAMTOR1	2.6	2.9	No	N/a	Unknown
Q59EK9	RUNDC3A	RUN domain-containing protein 3A	2.3	5.6	No	N/a	Unknown
P40121	CAPG	Macrophage-capping protein	2.2	1.9	No	Increased	Unknown
Q9NQ79	CRTAC1	Cartilage acidic protein 1	2.1	2.2	No	N/a	Unknown
Q9P2S2	NRXN2	Neurexin-2	1.9	2.5	No	N/a	Unknown
Q99435	NELL2	Protein kinase C-binding protein NELL2	1.8	3.9	No	N/a	Unknown
Q9HB90	RRAGC	Ras-related GTP-binding protein C	1.9	2.2	No	N/a	Unknown
Q86Y82	STX12	Syntaxin-12	1.5	2.0	No	N/a	Unknown

Proteins listed in order of fold change enrichment in EOAD; separated into previously confirmed plaque proteins, associated with Aβ or APP, and novel. “Previously confirmed plaque proteins” were determined by published immunohistochemistry evidence of protein presence in plaque or by > 1.5 fold enrichment in plaque in comparison to neighboring non-plaque tissue in late onset AD or preclinical AD [44]. Difference in AD tissue was determined by comparison with 33 previous proteomic studies of human AD brain tissue. “Mediates Aβ pathology?” determined by literature searches for “Alzheimer’s disease and gene ID or protein name”. Protein was designated as mediating Aβ pathology if altering protein expression in transgenic animal models or cell culture affected amyloid pathology

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ISSN: 2051-5960

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