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 AM, Bulfinch L, Sullivan PM, and MJ LaDu. Effect of Aβ structure and human apoE isoform on primary co-cultures of neurons and glia. Neurobiol. of Aging. 28:1139-1147, 2007. abstract | pdf

Trommer BL, Shah C, Gamkrelidze G, Yun SH, Pasternak ES, Stine B, Manelli A, Sullivan P, Pasternak JF, and MJ LaDu. Apolipoprotein E isoform-specific effects on LTP: blockade by oligomeric amyloid-β. Neurobiol Dis. 18(1):75-82, 2005.
abstract | pdf

Yun SH, Park KA, Sullivan P, Pasternak JF, LaDu MJ, and BL Trommer. ACh receptors supress hippocampal LTP in wild type but not apoE4 targeted replacement mice. J. Neurosci. Res. 82(6):771-777, 2005.
abstract | pdf

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

Rebeck, G.W., Kindy, M., and M.J. LaDu. Apolipoprotein E and Alzheimer's disease: the protective effect of apoE2 and E3. J Alzheimers Dis. 4(6):145-154, Review, 2002.
abstract | pdf

Jordan J, Galindo MF, Miller RJ, Reardon CA, Getz GS, and MJ LaDu. Isoform-specific effect of apolipoprotein E on cell survival and β-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures. J Neurosci. 18(1):195-204, 1998.
abstract | pdf

Puttfarcken PS, Manelli AM, Falduto MT, Getz GS, and MJ LaDu. Effects of apolipoprotein E on neurite outgrowth and β-amyloid induced toxicity in developing rat primary hippocampal cultures. J Neurochem. 68(2):760-769, 1997
abstract | pdf

Aβ-induced Neurotoxicity is Enhanced by ApoE4

In Vitro Neuronal Dysfunction and Death:
Healthy Neurons (left), Distressed Neurons (right)

Figure 1. Primary neurons.

ApoE4 is Neuotoxic:
ApoE3 prevents Aβ-induced neurotoxicity

[Jordan, 1997]

Figure 2.

Primary Mouse Neuron/Glia Co-Culture Model:
Human ApoE isoforms from targeted replacement mice glia

[Attribution: Katie Youmans]

Figure 3.

Aβ-42 Induced Neurotoxicity with E3 Glia:
Oligomers > Fibril

[Attribution: Katie Youmans; data taken from Manelli, 2008]

Figure 4.

ApoE Isoform Effects on Oligomeric Aβ1-42 Induced Neurotoxicity

[Manelli, 2008]

Figure 5. Neurons cultured with the apoE4-expressing glia were more susceptible to Aβ1-42 oligomer-induced death when compared to WT, KO, E2, and E3 glia (left). The increased toxicity seen with E4, when compared to the absence of apoE, suggests a gain of toxic function (right).

ApoE Isoform Effects on Oligomeric Aβ1-42-Induced:
Inhibition of LTP
E4 > KO = E3 > E2

[Trommer, NBD, 2005]

Figure 6. Treatment with 100nM Aβ1-42 oligomers (left) completely inhibited LTP in the E4 mice, with no effect in the KO or E3 mice. When the oligomer concentration was raised to 400nM, E2 LTP was unaffected while KO and E3 LTP were abolished. Results suggest a gain of toxic function for E4 and a gain of protective function for E2.

Related Publications

Manelli AM, Bulfinch L, Sullivan PM, and MJ LaDu. Effect of Aβ structure and human apoE isoform on primary co-cultures of neurons and glia. Neurobiol. of Aging. 28:1139-1147, 2007.
abstract | pdf

Rebeck, G.W., Kindy, M., and M.J. LaDu. Apolipoprotein E and Alzheimer's disease: the protective effect of apoE2 and E3. J Alzheimers Dis. 4(6):145-154, Review, 2002.
abstract | pdf

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