Skip to main content

Table 1 Effect of apoE isoform on soluble exogenous apoE/Aβ complex levels

From: Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk

Study Human apoE source Aβ source apoE:Aβ Molar Ratio Detection Method Results
Strittmatter et al, 1993 [29, 30] Human CSF (NAD & AD) Syn. Aβ40, 1-28, 12-28 * (100μl CSF:2.5mM) SDS-PAGE (Reducing), WB apoE binds to Aβ40, 1-28, 12-28
Human plasma (Purified) Syn. Aβ40 1:170 SDS-PAGE (Non-reducing), WB apoE4/Aβ > apoE3/Aβ Stability at 4.6 pH = apoE3/Aβ > apoE4/Aβ (<10% apoE binds Aβ)
Wisniewski et al, 1993 [31] Human CSF (NAD & AD) Syn. Aβ40, Aβ42 * (50μg CSF:2μg/ml) SDS-PAGE (Reducing), WB apoE/Aβ at 34kDa
Sanan et al 1994 [32] Human plasma (Purified) Syn. Aβ28 1:139 SDS-PAGE (Non-reducing), WB apoE3/Aβ > apoE4/Aβ
LaDu et al, 1994 [33] HEK293 (CM) Syn. Aβ40 1:357   apoE3/Aβ > apoE4/Aβ
LaDu et al, 1995 [34] HEK293 (Purified & CM), Human plasma (Native & purified) Syn. Aβ40 1:357 SDS-PAGE (Non-reducing), WB CM & plasma (native): apoE3/Aβ40 > apoE4/Aβ40 Purified apoE (both sources): apoE3/Aβ40 = apoE4/Aβ40
Castano et al, 1995 [35] Recombinant # Syn. Aβ40 1:169 SDS-PAGE (Non-reducing), WB apoE3/Aβ40 at 40kDa
Naslund et al, 1995 [36] Recombinant # Syn. Aβ40, Aβ42 1:136 SDS-PAGE (Non-reducing & reducing), WB Non-reducing: apoE3/Aβ = apoE4/Aβ Reducing: higher molecular mass complexes
Golabek et al, 1995 [37] Recombinant # Syn. Aβ40 1:8.5 SDS-PAGE (Non-reducing), WB apoE/Aβ at >36kDa
Golabek et al, 1996 [38] Recombinant # Syn. Aβ40 * (0-150nM:2.5pmol) Solid plate assay apoE2/Aβ = apoE3/Aβ = apoE4/Aβ
Shuvaev & Siest et al, 1996 [39] Human plasma (Purified) Syn. Aβ40 1:130 Surface plasmon resonance apoE3/Aβ > apoE4/Aβ = apoE2/Aβ(↑ apoE3/Aβ with ↑ salt concentration & unaffected in pH 6-8)
Chan et al, 1996 [40] Ecoli (Purified), Human plasma (Purified) Syn. Aβ40 1:3-1:11 SDS-PAGE (Non-reducing), WB, Gel filtration apoE4/Aβ = apoE3/Aβ = apoE2/Aβ(Both sources gave same results, Aβ & apoE tetramer co-migrate)
Zhou et al, 1996 [41] RAW264 (CM) Syn. Aβ40 1:170 SDS-PAGE (Non-reducing), WB apoE3/Aβ >> apoE4/Aβ (ND)
LaDu et al, 1997 [42] HEK293 (CM), Human plasma (Native & Purified), rat & rabbit apoE (native) Syn. Aβ40 1:357 (CM), 1:715 (Plasma) SDS-PAGE (Non-reducing), WB Native: apoE2/Aβ = apoE3/Aβ = rabbit apoE/Aβ > apoE4/Aβ (ND) = rat apoE/Aβ Purified: apoE2/Aβ = apoE3/Aβ > apoE4/Aβ (ND) (Both CM & human plasma - native gave same results)
Yang et al, 1997 [43] CHO (CM), Human plasma Syn. Aβ40 1:97 (CM), 1:850 (Plasma) SDS-PAGE (Non-reducing), WB apoE3/Aβ = apoE2/Aβ >> apoE4/Aβ (ND) (Both sources gave same results)
Aleshkov et al, 1997 [44] BHK21 (CM), Recombinant # (Lipidated), Human plasma Syn. Aβ40 1:126 SDS-PAGE (Non-reducing), WB Recombinant & CM (apoE monomer): apoE2/Aβ > apoE3/Aβ >> apoE4/Aβ Plasma: apoE3/Aβ > apoE4/Aβ
Pillot et al, 1997 [45] Recombinant # Syn. Aβ29-40/42 1:5-1:100 SDS-PAGE (Non-reducing), WB apoE2/Aβ = apoE3/Aβ > apoE4/Aβ (ND) (Dose dependent ↑ complex with ↑ ratio Aβ:apoE3 or apoE2)
Russo et al, 1998 [46] Human plasma apoE # Syn. Aβ42, Human Aβ (Brain) * (17.7pmol:100μM) IP with SDS-PAGE (Non-Reducing?), WB apoE/Aβ complex at 40kDa
Pillot et al, 1999 [47] Recombinant # Syn. Aβ29-40, Aβ29-42 1:50 SDS-PAGE (Non-reducing), WB CTF-apoE/Aβ > NTF-apoE/Aβ (ND)
Yamauchi et al, 1999 [48] Recombinant # (Non-lipidated & lipidated) Syn. Aβ42 1:2-1250 ELISA apoE2/Aβ > apoE3/Aβ > apoE4/Aβ(No differences in lipidated vs. non-lipidated in apoE isoform)
Aleshkov et al, 1999 [49] BHK1 (CM) Syn. Aβ40 1:125 SDS-PAGE (Non-reducing), WB apoE2/Aβ = apoE2-Thr194-Ala/Aβ = apoE4-Arg158-cys/Aβ
Golabek et al, 2000 [50] Recombinant # Human plasma (Purified) Syn. Aβ40 1:8.5 SDS-PAGE (Non-reducing), WB Recombinant: NTF-apoE3/Aβ > CTF-apoE3/Aβ Plasma: apoE/Aβ at 38kDa
Tokuda et al, 2000 [51] RAW264 & HEK293 (CM, delipidated), Sf9 insect cells (Delipidated & lipidated) Syn. Aβ40, Aβ42 * (0-150nM/2.5pmol) ELISA CM & Sf9 (Lipidated): apoE3/Aβ > apoE4/Aβ All sources (Delipidated): apoE3/Aβ = apoE4/Aβ (apoE/Aβ: CM > Sf9 lipidated)
Drouet et al, 2001 [52] Ecoli (Purified) Syn. Aβ29-40 1:100 SDS-PAGE (Non-reducing), WB apoE/Aβ-CTF: apoE2/Aβ = apoE3/Aβ > apoE4/Aβ (ND)
Zhou et al, 2002 [53] RAW264 (CM), CSF (NAD E3/3, PAD E3/4, AD E4/4) Syn. Aβ40 1:250 (CM), * (CSF) (70μl CSF:100μM) co-IP, SDS-PAGE (Non-reducing), WB CM: apoE3/Aβ >> apoE4/Aβ CSF: APOE33/Aβ > APOE34/Aβ = APOE44/Aβ (ND) (With BMEless apoE3/Aβ)
Bentley et al, 2002 [54] HEK293 (CM) Syn. Aβ40 1:340 SDS-PAGE (Non-reducing), WB apoE3/Aβ > apoE4/Aβ = apoE3-Ala-112/Aβ = apoE4-Lys-112/Aβ (ApoE3-Thr-61/Aβ = apoE4-Thr-61/Aβ = no complex)
Gylys KH et al, 2003 [55] Recombinant # (Lipidated) Syn. Aβ40 1:5.6 SDS-PAGE (Non-reducing), WB apoE3/sAβ > apoE3/agg Aβ
Manelli et al, 2004 [56] HEK293 (CM) Syn. Aβ42 1:33 SDS-PAGE (Non–reducing), WB apoE3/oAβ > apoE3/Aβ fibrils > apoE4/oAβ > apoE4/Aβ fibrils
Phu et al, 2005 [57] Recombinant # Syn. AEDANS-F4C- Aβ42 1:1 FRET Soluble complex: CTF-apoE/Aβ
Stratman et al, 2005 [58] Recombinant # (Lipidated) Syn. Aβ40 1:500 ELISA Intermediate agg Aβ40: apoE4/Aβ >> apoE2/Aβ = apoE3/Aβ
Morikawa et al, 2005 [59] Immortalized astrocytes apoE-TR (CM immuno-purified), Primary astrocytes GFAP-apoE-Tg (CM Immuno-purified) Syn. Aβ40 1:4.5-22.5 SDS-PAGE (Reducing & non-reducing), WB (Physiological buffer in non - reducing) Reducing: apoE3/Aβ > apoE4/Aβ Non-reducing: apoE3/Aβ = apoE4/Aβ
Wellnitz et al, 2005 [60] N2a (CM) Syn. Aβ42 1:0.1-1000 SDS-PAGE (Reducing), WB CTF-apoE/hexameric Aβ: apoE4/Aβ > apoE3/Aβ = apoE2/Aβ
Petrlova et al, 2011 [61] Ecoli (Purified & lipidated) Syn. Aβ40 1:3.3 EPR spectroscopy Purified apoE: apoE3/oAβ > apoE4/oAβ Lipidated apoE: apoE3/Aβ > apoE4/Aβ (CTF apoE bind Aβ)
Cerf et al, 2011 [62] Ecoli (Purified) Syn. Aβ42 1:25-100 SDS-PAGE (Non-reducing), WB apoE monomers/agg Aβ: apoE3/Aβ = apoE4/Aβ (Stabilize oAβ42: apoE4 > apoE3)
Hashimoto et al, 2012 [27] Immortalized astrocytes apoE-TR (CM immuno-purified) Syn. Aβ42 1:0.083 SDS-PAGE (Reducing), WB No complex measured
Lipidated apoE stabilizes oAβ42: apoE4 > apoE3 > apoE2
LaDu et al, 2012 [63] Human Plasma (NAD), Rat Astrocyte (CM, isolated, purified delipidated) Syn. Aβ40 1:5-16 (Plasma); 1:36 (Rat ACM); 1:357 (Rat isolated & purified) SEC, SDS-PAGE (Non–reducing), WB Aβ co-elutes with apoE containing lipoproteins: Human plasma (70%) > rat ACM (53%) Monomer apoE/Aβ (45kDa) & dimer apoE/Aβ 97kDa : rat isolated > rat purified
Ly et al, 2013 [64] Ecoli (Purified) Syn. Aβ40 1-4:1, 1:2 Laser fluorescence spectroscopy Stable complex- apoE3L-Cys-264/oAβ > apoE4-Cys-264/oAβ (apoE3L means "apoE3 like" with Cys112-Ser)
Tai et al, 2013 [4] HEK293 (CM) Syn. Aβ42 1:0.005-50 ELISA Total complex: apoE2/Aβ = apoE3/Aβ = apoE4/Aβ SDS stable: apoE2/Aβ > apoE3/Aβ > apoE4/Aβ pH=5: apoE2/Aβ = apoE3/Aβ > apoE4/Aβ
Verghese et al, 2013 [65] Recombinant # (Lipidated) APP H4 neuroglioma (CM), Syn. Aβ40/42 1:0.02-0.05 (CM), 1:0.2-1 (Syn.) Density gradient ultracentrifugation, SEC, ELISA, FCS Monomeric Aβ free (95-97%) >> apoE3/Aβ = apoE4/Aβ (Lipidated apoE poorly binds binds Aβ)
Immortalized astrocytes apoE-TR (CM immuno-purified), Primary astrocytes GFAP-apoE-Tg (CM Immuno-purified) APP H4 neuroglioma (CM), 7PA2 cells (CM) 1:0.04 (H4), 1:0.05 (7PA2) SEC, ELISA, FCS Higher order Aβ species (free) >> apoE3/Aβ = apoE4/Aβ
Human CSF (Pooled non-concentrated, NAD) APP H4 neuroglioma (CM) * (800μl CSF:50ng/ml) SEC 95% in vitro Aβ (free) = in vivo Aβ (free) >> apoE/Aβ
  1. #, Commercially purchased recombinant human apoE; *, apoE:Aβ ratio unknown; Lipidated apoE is either with POPC, reconstituted "HDL" or plasma lipoprotein.
  2. ACM, Astrocyte conditioned media; AD, Alzheimer’s disease; agg Aβ, Aggregated Aβ; BME, β - mercaptoethanol; CSF, Cerebrospinal fluid; CM, Conditioned media; co-IP, co - immunoprecipitation; CTF, C-terminal fragment; EPR, Electron paramagnetic resonance; ELISA, Enzyme-linked immunosorbent assay; FCS, Fluorescence correlation spectroscopy; FRET, Fluorescence resonance energy transfer; IP, Immunoprecipitation; NAD, Non-AD or non-dementia control; ND, Not detectable; NTF, N-terminal fragment; oAβ, Oligomeric Aβ; PAD, Probable AD; PAGE, Polyacrylamide gel electrophoresis; sAβ, Soluble Aβ; Sf9, Spodoptera frugiperda insect cells; SDS, Sodium dodecyl sulfate; SEC, Size exclusion chromatography; Syn, Synthetic; Tg, Transgenic; TR, Target replacement; WB, western blot.