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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
  1. 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