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More than 20 years ago, a polymorphism in the apolipoprotein E (apoE) gene was identified as the primary risk factor for late-onset Alzheimer disease (AD).1 Individuals carrying the ε4 isoform of apoE (apoE4) are at significantly greater risk for AD compared with apoE3 carriers, whereas the apoE2 allele is associated with reduced AD risk.2 Despite 2 decades of research into the mechanisms by which apoE4 contributes to disease pathogenesis, a seemingly simple question remains unresolved: is apoE good or bad for brain health? The answer to this question is essential for the future development of apoE-directed therapeutics.
Lane-Donovan C, Herz J. Is Apolipoprotein E Required for Cognitive Function in Humans?Implications for Alzheimer Drug Development. JAMA Neurol. 2014;71(10):1213-1215. doi:10.1001/jamaneurol.2014.2013