Table 1 Biochemical and biophysical evidence of interactions of Aβ with other proteins, and their presence in senile plaque and potential for AD biomarker

Immunoglobulins

Ig alpha-1 chain C region

[50]^a

[52, 56]^b,d

[32, 33, 59, 60]^f,j†,g,h

HC^f, FCtx^j†, HC^g, CCtx and Cve^h

[61]:↑P

[62]:↑C

Ig gamma-1 chain C region

[50]^a

[51, 52, 56]^e,b,d

[26, 32, 33, 59]^i,f,j†,g

F-tCtxⁱ, HC^f, FCtx^j†, HC^g

[61]:↓P

Ig gamma-2 chain C region

[50]^a

[52, 56]^b,d

[26, 32, 33, 59]^i,f,j†,g

F-tCtxⁱ, HC^f, FCtx^j†, HC^g

Ig gamma-3 chain C region

[50]^a

[52, 56]^b,d

[26, 32, 33, 59]^i,f,j†,g

F-tCtxⁱ, HC^f, FCtx^j†, HC^g

Ig kappa chain C region

[50]^a

[51, 52, 56]^e,b,d

[26, 32, 33, 59, 60]^i,f,j†,g,h

F-tCtxⁱ, HC^f, FCtx^j†, HC^g, CCtx and Cve^h

[61]:↑P

Ig mu chain C region

[50]^a

[51, 52, 56]^e,b,d

[32, 33]^f,j†

HC^f, FCtx^j†

[61]:↓P

Immunoglobulin heavy constant alpha 2

[51, 56]^e,d

Immunoglobulin heavy variable 3-7

[51, 53]^e,j

Complement system

Alpha-1-antichymotrypsin

[50, 63,64,65]^a,k,l,n

[56]^d

[28, 31, 32, 59, 60, 66, 67]^{q,r,f,g,h,s,t}

FCtx and TCtx^r, HC^f,g, CCtx and Cve^h, PreFCtx^s

[68]:↑P

[69]:↑C

C4b-binding protein alpha chain

[52, 53, 56]^b,j,d

[28, 32, 33]^q,g,j†

HC^f, FCtx^j†

Complement C1q subcomponent subunit A/subunit B/subunit C

[50, 70]^a,u

[51, 56, 71, 72]^e,d,v,w

[26, 28, 31,32,33, 59, 60, 66, 73]^{i,q,r,f,g,j†,h,s,x}

F-tCtxⁱ, FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, TLb^x; CP^x

[74]:↓C (subunit B/C)

Complement C1r subcomponent

[51,52,53, 56]^e,b,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Complement C1s subcomponent

[51,52,53, 56]^e,b,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

[74]:↓C

Complement C3

[50]^a

0.3 μM (Aβ42PF)^a

[51,52,53, 56, 72, 75]^e,b,j,d,w,y

[26, 28, 31,32,33, 59, 60, 66, 73]^{i,q,r,f,j†,g,h,s,x}

F-tCtxⁱ, FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, TLb^x; CP and DP^x

[76, 77]:↑P/S, [78]:↑C

Complement C4-A/C4-B

[50]^a

[51,52,53, 56, 72]^e,b,j,d,w

[26, 31, 32, 59, 60, 66, 73] ^{i,r,f,g,h,s,x}

F-tCtxⁱ, FCtx and TCtx^r, HC^f,g, CCtx and Cve^h, PreFCtx^s, TLb^x; CP and DP^x

[61, 76]:↑↓S, [79]:↑C

Complement C5

[53, 56, 72]^j,d,w

[32, 33]^f,j†

HC^f, FCtx^j†

Complement component C7

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Complement component C8 gamma chain

[53, 56]^j,d

[32, 33, 60]^f,j†,h

HC^f, FCtx^j†, CCtx and Cve^h

Complement component C9

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Complement factor H

[51,52,53, 56]^e,b,j,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

[61, 76]:↑P/S

Complement factor H-related protein 5

[50]^a

[51, 56]^e,d

Inter-alpha-trypsin inhibitor heavy chain H4

[50]^a

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

[61]:↓P,

[80]:↑C

Monocyte differentiation antigen CD14

[50]^a

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

Plasma protease C1 inhibitor

[51, 56]^e,d

[32, 33, 60]^f,j†,h

HC^f, FCtx^j†, CCtx and Cve^h

Lipid metabolism/transport

Apolipoprotein A-I

[50, 81,82,83,84]^{a,z,a†,b†,d†}

3 μM (Aβ42PF)^a,

6 nM (Aβ40M)^d†

[51,52,53, 56, 85]^e,b,j,d,e†

[32, 33, 59, 60, 66, 86]^{f,j†,g,h,s,f†}

HC^f, FCtx^j†, HC^g,, CCtx and Cve^h, PreFCtx^s, HC^f†

[87,88,89]:↓ S/P, [90]:↑C

Apolipoprotein A-II

[50, 82]^a,a†

[51,52,53, 56, 85]^e,b,j,d,e†

[32, 33]^f,j†

HC^f, FCtx^j†

Apolipoprotein A-IV

[50, 83]^a,b†

[51,52,53, 56]^e,b,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

[88]:↑P,

[80]: ↑C

Apolipoprotein B-100

[50]^a

[52]^b

[32, 33, 60]^f,j†,h

HC^f, FCtx^j†, CCtx and Cve^h

[76, 89]:↑↓S

Apolipoprotein C-I

[51, 52, 56]^e,b,d

[91]:↓C

Apolipoprotein C-II

[92]^g†

[51, 52]^e,b

[32, 33]^f,j†

HC^f, FCtx^j†

Apolipoprotein C-III

[51,52,53, 56]^e,b,j,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

Apolipoprotein C-IV

[50]^a

[51, 56]^e,d

Apolipoprotein D

[50]^a

[51, 52, 56]^e,b,d

[32, 33, 59, 60, 66, 93, 94]^{f, j†,g,h,s,h†,i†}

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, CCtx and HC^h†,i†; DP, around CP, and CAA^h†,i†

[95, 96]:↓C

Apolipoprotein E

[50, 63, 82,83,84]^{a,k,a†,b†,d†}

3 nM (Aβ42PF)^a,

19 nM (Aβ40M)^d†

[51,52,53, 56, 85]^e,b,j,d,e†

[28, 31,32,33, 59, 60, 66, 94] ^{q,r,f,j†,g,h,s,i†}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, CCtx and HC^i†; CP, DP, and CAA^i†

[76]:↑S, [78, 97, 98]:↑↓C

Apolipoprotein L1

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Beta-2-glycoprotein 1

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

Clusterin (a.k.a, ApoJ)

[50, 81,82,83, 99, 100]^{a,z,a†,b†,k†,l†}

4.8 nM (Aβ40M)^k†,

2 nM (AβM)^l†

[51,52,53, 56, 85]^e,b,j,d,e†

[28, 31,32,33, 59, 60, 66, 73, 101]^{q,r,f,j†,g,h,s,x,n†}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, TLb^x, EntCtx^n†;CP^x,n†

[102]:↓P,

[78]:↑C

Phospholipid transfer protein

[50]^a

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

Prostaglandin-H2 D-isomerase

[50]^a

[51, 56]^e,d

[32, 59, 60, 66]^f,g,h,s

HC^f,g, CCtx and Cve^h, PreFCtx^s

[62, 103]:↑↓C

Serum amyloid A-4 protein

[50]^a

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Blood coagulation/hemostasis

Adipocyte enhancer-binding protein 1

[51, 56]^e,d

Alpha-1-antitrypsin

[50]^a

[51, 52, 56]^e,b,d

[28, 31,32,33, 59, 60, 66]^{q,r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[89, 102, 104]:↑↓ P/S, [80, 96]:↑↓C

Alpha-2-macroglobulin

[84, 105, 106]^{d†,r†,s†}

0.34 μM (Aβ40M)^d†,

0.35 μM (Aβ40M)^r†, 38 μM (Aβ42M)^s†

[53, 56]^j,d

[28, 31,32,33, 59, 60, 66]^{q,r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[61, 76, 107]:↑ P/S

Angiotensinogen

[50]^a

[51, 56]^e,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

Antithrombin-III

[50]^a

0.6 μM (Aβ42PF)^a

[51, 53, 56]^e,j,d

[32, 33, 59, 108]^{f,j†,g,t†}

HC^f, FCtx^j†, HC^g, CCtx^t†; CP^t†

[69, 80]:↑C

Beta-1,4-glucuronyltransferase1

[51, 56]^e,d

[32, 59]^f,g

HC^f,g

Carboxypeptidase B2

[53, 56]^j,d

[33]^j†

FCtx^j†

Coagulation factor V

[50]^a

[51, 56]^e,d

[33]^j†

FCtx^j†

Coagulation factor X

[51, 52, 109]^e,b,u†

[33]^j†

FCtx^j†

Coagulation factor XII

[110]^v†

[53, 56, 111]^j,d,w†

[32, 33, 66]^f,j†,s

HC^f, FCtx^j†, PreFCtx^s

Fibrinogen alpha−, beta−, and gamma−chain

[50, 112]^a,x†

26 nM (Aβ42M)^x†

[51, 52, 56]^e,b,d

[31,32,33, 59, 60, 66, 113]^{r,f,j†,g,h,s,y†}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, FCtx^y†; CAA^y†

[77, 88, 89]:↑↓ P/S, [98]:↑C

Fibronectin

[50]^a

[51,52,53, 56, 109]^{e,b,j,d, u†}

[32, 33, 59, 66]^j†,f,g,s

HC^f, FCtx^j†, HC^g, PreFCtx^s

[89]:↑S

Growth arrest-specific protein 6

[51, 56]^e,d

[33]^j†

FCtx^j†

[114]:↑C

Heparin cofactor 2

[50]^a

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

Histidine-rich glycoprotein

[50]^a

[52, 56]^b,d

[32, 33, 59]^j†,f,g

FCtx^j†, HC^f,g

[76]:↑S

Hyaluronan-binding protein 2

[52, 56]^b,d

[31,32,33]^r,f,j†

FCtx and TCtx^r, HC^f, FCtx^j†

Kininogen-1

[51, 53, 56]^e,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Plasminogen

[51, 53, 109]^e,j,u†

[32, 33]^f,j†

HC^f, FCtx^j†

[78]:↑C

[88]:↓P

Prothrombin

[50]^a

[51,52,53, 56]^e,b,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Vitamin K-dependent protein S

[51,52,53, 56]^e,b,j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Metabolism

Alpha-enolase

[50]^a

[51, 56]^e,d

[32, 33, 59, 60, 66, 115]^{f,j†,g,h,s,z†}

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

Glyceraldehyde-3-phosphate dehydrogenase

[50, 63]^a,k

[51, 56, 116]^e,d,a‡

[31, 32, 59, 60, 66]^r,f,g,h,s

FCtx and TCtx^r, HC^f,g, CCtx and Cve^h, PreFCtx^s

Phosphoglycerate kinase 1

[50]^a

[56]^d

[31,32,33, 59, 60, 66]^{r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

Procollagen C-endopeptidase enhancer 1

[50]^a

[51, 56]^e,d

Molecular transport

Haptoglobin

[50]^a

[53, 56]^j,d

[32, 33, 59, 60, 66]^f,j†,g,h,s

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[76]:↑S

Hemoglobin subunit alpha/subunit beta

[50]^a

[51, 56]^e,d

[31,32,33, 59, 60, 66]^{r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[76]:↑S

Hemopexin

[53, 56]^j,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

[104]:↑P

Inter-alpha-trypsin inhibitor heavy chain H2

[50]^a

[53, 56]^j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Serotransferrin

[50]^a

[53, 56]^j,d

[31,32,33, 59, 66]^r,f,j†,g,s

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, PreFCtx^s

Serum albumin

[50, 83, 117,118,119,120]^{a,b†, b‡,c‡,d‡,e‡}

1–100 nM (Aβ40O)^b‡, 1.7 μM (Aβ42M)^c‡, 5 μM (Aβ40M)^d‡, ~0.1–1 mM (Aβ40M)^e‡

[51,52,53, 56, 109]^e,b,j,d,u†

[31,32,33]^r,f,j†

FCtx and TCtx^r, HC^f, FCtx^j†

[61]:↑P, [62, 98]:↑↓C

Transthyretin

[81, 121]^z,f‡

~28 nM (Aβ40M/O)^f‡

[51, 52, 56, 121] [122]^{e,b,d,f‡,h‡}

~28 nM (Aβ42F)^f‡

[32, 33, 66]^f,j†,s

HC^f, FCtx^j†, PreFCtx^s

[76]:↑S, [78]:↑C

Vitamin D-binding protein

[51,52,53, 56]^e,b,j,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

[102]:↑P,

[78]:↑C

Neural proteins

Amyloid-like protein 1

[51, 52, 56]^e,b,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

[62, 123]:↑↓C

Brevican core protein

[51, 109]^e,u†

[32, 33, 59, 60, 66]^f,j†,g,h,s

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

Neural cell adhesion molecule 1

[51, 56]^e,d

[31,32,33, 59, 60, 66]^{r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[103]:↑C

Neurocan core protein

[51, 109]^e,u†

11.7 nM (Aβ42F)^e

[32, 33, 59, 60, 66]^f,j†,g,h,s

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

Neurosecretory protein VGF

[51, 56]^e,d

[32, 33, 59, 66]^f,j†,g,s

HC^f, FCtx^j†, HC^g, PreFCtx^s

[79, 90, 124, 125]:↓C

ProSAAS

[51, 52, 56]^e,b,d

[32, 33, 59, 60, 66]^f,j†,g,h,s

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[62, 78]:↑↓C

Cell adhesion, extracellular matrix, and proteoglycans

Agrin

[51, 109, 126]^e,u†,i‡

3.5 nM (Aβ42F)^e

[32, 33, 59, 60, 66, 126]^{f,j†,g,h,s,j‡}

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s, FCtx^j‡; CP, DP, and CCA ^j‡

[127]^k‡

Basement membrane-specific heparan sulfate proteoglycan core protein

[51, 56]^e,d

[32, 33, 59, 60, 66]^f,j†,g,h,s

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

Cartilage acidic protein 1

[50]^a

[51, 56]^e,d

[32, 33, 59, 60]^f,j†,g,h

HC^f, FCtx^j†, HC^g, CCtx and Cve^h

Collagen alpha-1(XVIII) chain

[50]^a

[51, 56]^e,d

[32, 33, 59, 66]^f,j†,g,s

HC^f, FCtx^j†, HC^g, PreFCtx^s

Decorin

[50, 128]^a,l‡

[51, 56, 109]^e,d,u†

[32, 33, 129]^f,j†,n‡

HC^f, FCtx^j†, HC^n‡; CP^n‡

Desmoplakin

[50]^a

[51, 56]^e,d

[32, 33, 59, 66]^f,j†,g,s

HC^f, FCtx^j†, HC^g, PreFCtx^s

[61]:↑P

EGF-containing fibulin-like extracellular matrix protein 1

[50]^a

[51, 52]^e,b

[32]^f

HC^f

[74]:↓C

Extracellular matrix protein-1

[53, 109]^j,u†

[32]^f

HC^f

Extracellular matrix protein-2

[50]^a

[51, 56]^e,d

[32]^f

HC^f

Fibulin-1

[50, 83]^a,b†

[51,52,53, 56]^e,b,j,d

[32]^f

HC^f

[89]:↑S

Galectin-3-binding protein

[50]^a

[51, 56]^e,d

[32, 33, 60, 66]^f,j†,h,s

HC^f, FCtx^j†, CCtx and Cve^h, PreFCtx^s

Glypican-1

[51, 109, 130]^e,u†q‡

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

Microfibril-associated glycoprotein 4

[50]^a

[56]^d

[33, 66]^j†,s

FCtx^j†, PreFCtx^s

Mimecan

[50]^a

[51, 52, 56]^e,b,d

[33, 66]^j†,s

FCtx^j†, PreFCtx^s

Osteomodulin

[51, 56]^e,d

Osteopontin

[51, 56]^e,d

[32, 33]^{f, j†}

HC^f, FCtx^j†

[123]:↑C

Prolargin

[50]^a

[51, 56]^e,d

[32, 33]^{f, j†}

HC^f, FCtx^j†

SPARC-like protein 1

[51, 52, 56, 109]^e,b,d,u†

6.2 nM (Aβ42F)^e

[32, 33, 59, 60]^f,j†,g,h

HC^f, FCtx^j†, HC^g, CCtx and Cve^h

[98]:↑C

Vitronectin

[50, 83]^a,b†

[51,52,53, 56]^e,b,j,d

[32, 33, 59, 101, 131]^{f,j†,g,n†,s‡}

HC^f, FCtx^j†, HC^g, EntCtx^n†,s‡; CP^n†,s‡

[76]:↑S

Other proteins

Actin, cytoplasmic 1

[50]^a

[51, 56]^e,d

[32, 59, 60, 115]^f,g,h,z†

HC^f,g, CCtx and Cve^h

Alpha-1B-glycoprotein

[53, 56]^j,d

[32, 33]^f,j†

HC^f, FCtx^j†

Alpha-2-HS-glycoprotein

[51,52,53, 56]^e,b,j,d

[32]^f

HC^f

[62, 79]:↓C, [88]:↓P

Beta-Ala-His dipeptidase

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

[90]:↓C

Cystatin-C

[50, 132, 133]^a,t‡,u‡

11–17 nM (Aβ40/42M)^u‡

[51, 52, 56]^e,b,d

[31,32,33, 59, 60, 66]^{r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[91, 96, 97]:↑↓C

Dermcidin

[50]^a

[51, 56]^e,d

[31,32,33, 59, 66]^r,f,j†,g,s

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, PreFCtx^s

Dickkopf-related protein 3

[51, 52, 56]^e,b,d

26.2 nM (Aβ42F)^e

[32, 33, 59, 134]^{f,j†,g,r‡}

HC^f, FCtx^j†, HC^g,r‡; CP and DP^r‡

[134]^v‡

Gelsolin

[50, 135,136,137]^{a,w‡,x‡,y‡}

1.38 μM (Aβ40M)^w‡

[51,52,53, 56]^e,b,j,d

[31,32,33, 59, 60, 66]^{r,f,j†,g,h,s}

FCtx and TCtx^r, HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[89]:↑S

Hepatocyte growth factor activator

[53, 56]^j,d

[33]^j†

FCtx^j†

Latent-transforming growth factor beta-binding protein 4

[50]^a

[51, 56]^e,d

[32]^f

HC^f

Protein AMBP

[51, 53, 56]^e,j,d

[32, 33]^{f, j†}

HC^f, FCtx^j†

Olfactomedin-like protein 3

[50]^a

[51, 56]

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

Secreted frizzled-related protein 3

[51, 56]^e,d

[32, 33]^f,j†

HC^f, FCtx^j†

Secretogranin-1

[51, 56]^e,d

[32, 33, 59]^f,j†,g

HC^f, FCtx^j†, HC^g

[62, 138]:↓C

Serum amyloid P-component

[50, 83, 139]^a,b†z‡

6 nM (Aβ40M)^z‡

[51, 56]^e,d

[28, 32, 33, 59, 60, 66]^{q,f,j†,g,h,s}

HC^f, FCtx^j†, HC^g, CCtx and Cve^h, PreFCtx^s

[61]:↑P