Welcome to Dr. Mary Jo LaDu's Research Lab!

Introduction

ApoE and the Brain

Native ApoE3 Binds Aβ with Higher Affinity than ApoE4

Characterization of CNS Lipoproteins

Structure and Function of Aβ1-42 Assemblies

Aβ-induced Neurotoxicity is Enhanced by ApoE4

Effects of ApoE that Modify Actions of Aβ are Mediated by ApoE Receptors

Metabolism of ApoE3 and E4 ± Aβ-42

Transgenic Mouse Models

Related Publications

Manelli, A.M., Stine Jr., W.B., Van Eldik, L.J., and M.J. Ladu. ApoE and Aβ1-42 interactions: effects of isoform and conformation on structure and function. J Mol Neurosci. 23:235-246, Review, 2004.
abstract | pdf

Bentley NM, LaDu MJ, Rajan C, Getz GS, and CA Reardon. Apolipoprotein E structural requirements for the formation of SDS-stable complexes with β-amyloid-(1-40): the role of salt bridges. Biochem J. 15;366(Pt 1):273-9, 2002.
abstract | pdf

Munson GW, Roher AE, Kuo YM, Gilligan SM, Reardon CA, Getz GS, and MJ LaDu. SDS-stable complex formation between native apolipoprotein E3 and β-amyloid peptides. Biochemistry. 26;39(51):16119-24, 2000.
abstract | pdf

Tokuda T, Calero M, Matsubara E, Vidal R, Kumar A, Permanne B, Zlokovic B, Smith JD, Ladu MJ, Rostagno A, Frangione B, and J Ghiso. Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid-β peptides. Biochem J. 1;348 Pt 2:359-65, 2000.
abstract | pdf

LaDu MJ, Lukens JR, Reardon CA, and GS Getz. Association of human, rat, and rabbit apolipoprotein E with β-amyloid. J Neurosci Res. 1;49(1):9-18, 1997.
abstract | pdf

LaDu MJ, Pederson TM, Frail DE, Reardon CA, Getz GS, and MT Falduto. Purification of apolipoprotein E attenuates isoform-specific binding to β-amyloid. J Biol Chem. 21;270(16):9039-42, 1995.
abstract | pdf

LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, and DE Frail. Isoform-specific binding of apolipoprotein E to β-amyloid. J Biol Chem. 23;269(38):23403-6, 1994.
abstract | pdf

Native ApoE3 Binds Aβ with Higher Affinity than ApoE4

ApoE3 has a greater affinity for both Aβ1-40 and Aβ1-42 than does apoE4, as measured by SDS-stable complex formation via gel-shift on SDS-PAGE (Figure 1, 2).

The isoform-specific interaction between apoE:Aβ is dependent on apoE conformation (native vs. purified). ApoE isolated from human plasma behaves the same as apoE isolated from HEK conditioned media. Both purified apoE3 and apoE4 have a comparable, lower affinities for Aβ1-40 (Figure 1).

The isoform-specific interaction between apoE:Aβ is dependent on Aβ conformations. ApoE3 has a greater affinity for oligomeric Aβ1-42 than for fibrillar Aβ1-42 (Figure 2).

ApoE Conformation and Isoform Effect
ApoE:Aβ1-40 Complex Formation

[LaDu, JBC, 1995]

Figure 1.

Lipoprotein-associated apoE: apoE3:Aβ > apoE4:Aβ

Purified apoE: apoE3:Aβ = apoE4:Aβ

Aβ Conformation and ApoE Isoform Effect
ApoE:Aβ1-42 Complex Formation

[Manelli, J. Mol. Neurosci., 2004]

Figure 2.

apoE3:oligomers > apoE3:fibrils

apoE3:oligomers and apoE3:fibrils > apoE4:oligomers and apoE4:fibrils

ApoE3/Aβ > ApoE4/Aβ-40 in Media of Treated Primary Neuron/Glia Co-cultures

[Jordan, 1997]

Figure 3.

Related publications:

LaDu MJ, Lukens JR, Reardon CA, and GS Getz. Association of human, rat, and rabbit apolipoprotein E with β-amyloid. J Neurosci Res. 1;49(1):9-18, 1997.
abstract | pdf

LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, and DE Frail. Isoform-specific binding of apolipoprotein E to β-amyloid. J Biol Chem. 23;269(38):23403-6, 1994.
abstract | pdf

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