Apolipoprotein E isoforms and regulation of the innate immune response in brain of patients with Alzheimer's disease

作者：Keene C Dirk; Cudaback Eiron; Li Xianwu; Montine Kathleen S; Montine Thomas J^*

来源：Current Opinion in Neurobiology, 2011, 21(6): 920-928.

DOI：10.1016/j.conb.2011.08.002

The largest genetic risk for late-onset Alzheimer's disease (AD) resides at the apolipoprotein E gene (APOE) locus, which has three common alleles (epsilon 2, epsilon 3, epsilon 4) that encode three isoforms (apoE2, apoE3, apoE4). The very strong association of the APOE epsilon 4 allele with AD risk and its role in the accumulation of amyloid beta in brains of people and animal models solidify the biological relevance of apoE isoforms but do not provide mechanistic insight. The innate immune response is consistently observed in AD and is a likely contributor to neuronal injury and response to injury. Here we review emerging data showing that apoE isoform regulation of multiple facets of the innate immune response in the brain may alter AD not only through amyloid beta-dependent mechanisms, but also through other, amyloid beta-independent mechanisms.

• 出版日期2011-12