Journal of Molecular Neuroscience

, Volume 23, Issue 3, pp 247–254 | Cite as

In vivo effects of apoE and clusterin on amyloid-β metabolism and neuropathology

  • David M. HoltzmanEmail author
Original Article


The ε4 allele of apolipoprotein E APOE is a risk factor for Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA), and the ε2 allele is associated with a decreased risk for AD. There is strong evidence to suggest that a major, if not the main, mechanism underlying the link between apoE and both AD and CAA is related to the ability of apoE to interact with the amyloid-β (Aβ) peptide and influence its clearance, aggregation, and conformation. In addition to a number of in vitro studies supporting this concept, in vivo studies with amyloid precursor protein (APP) transgenic mice indicate that apoE and a related molecule, clusterin (also called apolipoprotein J), have profound effects on the onset of Aβ deposition, as well as the local toxicity associated with Aβ deposits both in the brain parenchyma and in cerebral blood vessels. Taken together, these studies suggest that altering the expression of apoE and clusterin in the brain or the interactions between these molecules and Aβ would alter AD pathogenesis and provide new therapeutic avenues for prevention or treatment of CAA and AD.

Index Entries

Alzheimer’s disease apolipoprotein E clusterin amyloid 


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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  1. 1.Center for the Study of Nervous System Injury, Alzheimer’s Disease Research Center, Departments of Neurology, and Molecular Biology and PharmacologyWashington University School of MedicineSt. Louis

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