摘要
Genetic variation in apolipoprotein E(APOE)influences Alzheimer’s disease(AD)risk.APOEε4 alleles are the strongest genetic risk factor for late onset sporadic AD.The AD risk is dose dependent,as those carrying one APOEε4 allele have a 2-3-fold increased risk,while those carrying twoε4 alleles have a 10-15-fold increased risk.Individuals carrying APOEε2 alleles have lower AD risk and those carrying APOEε3 alleles have neutral risk.APOE is a lipoprotein which functions in lipid transport,metabolism,and inflammatory modulation.Isoform specific effects of APOE within the brain include alterations to Aβ,tau,neuroinflammation,and metabolism.Here we review the association of APOE with AD,the APOE isoform specific effects within brain and periphery,and potential therapeutics.
基金
supported by the National Institutes of Health(P30AG035982 and R00AG056600,USA)
the Peg Mc Laughlin fund(USA)。