Apolipoprotein E, Amyloid, and Alzheimer Disease

• Published in: Molecular interventions Vol. 2; no. 6; pp. 363 - 375
• Main Authors: Bales, K R, Dodart, J C, DeMattos, R B, Holtzman, D M, Paul, S M
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01-10-2002
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Amyloid - metabolism; Amyloid beta-Peptides - metabolism; Animals; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Central Nervous System - metabolism; Genetic Predisposition to Disease; Humans; Mice
• ISSN: 1534-0384; 1543-2548
• DOI: 10.1124/mi.2.6.363

The alleles for apolipoprotein E (apoE) represent important genetic risk factors for the most common late-onset forms of Alzheimer
disease (AD), with the ε 4 and ε 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-β
peptide (Aβ ) 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 Aβ 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.