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

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