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1 Neuroscience Discovery Research, Lilly Research Laboratories Indianapolis, IN 46285
2 Washington University School of Medicine, 660 S. Euclid Ave. St. Louis, MO 63110
Correspondence: Address correspondence to SMP. E-mail Paul_Steven_M{at}lilly.com; fax 317-277-1125.
The alleles for apolipoprotein E (apoE) represent important genetic risk factors for the most common late-onset forms of Alzheimer disease (AD), with the 
4 and 2 alleles increasing and decreasing the risk for developing AD, respectively. ApoE, a 34-kDa lipid transport protein, is predominantly expressed in the liver, but is also expressed in brain by microglia and astrocytes. Studies utilizing mouse models that mimic the neuropathology of AD have demonstrated an apoE isoform–dependent effect on amyloid-ß peptide (Aß ) deposition, fibrillization, and neuritic plaque formation. Taken together, these data support an important (and isoform-dependent) role for apoE in the pathogenesis of AD, most likely by altering Aß clearance and/or metabolism. Further elucidation of the exact cellular and molecular events mediating apoE isoform–dependent amyloid deposition could lead to novel therapeutic strategies for preventing or treating AD.
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