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 A...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.展开更多
Advancing age is a major risk factor for Alzheimer’s disease(AD).This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging.Correlative an...Advancing age is a major risk factor for Alzheimer’s disease(AD).This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging.Correlative and modeling studies can inform this question,but without a frm grasp of what drives aging and AD it is difcult to defnitively resolve this quandary.This review speculates over the relevance of a particular hallmark of aging,mitochondrial function,to AD,and further provides background information that is pertinent to and provides perspective on this speculation.展开更多
基金supported by the National Institutes of Health(P30AG035982 and R00AG056600,USA)the Peg Mc Laughlin fund(USA)。
文摘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The authors are supported by P30AG035982HMW is additionally supported by R00AG056600.
文摘Advancing age is a major risk factor for Alzheimer’s disease(AD).This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging.Correlative and modeling studies can inform this question,but without a frm grasp of what drives aging and AD it is difcult to defnitively resolve this quandary.This review speculates over the relevance of a particular hallmark of aging,mitochondrial function,to AD,and further provides background information that is pertinent to and provides perspective on this speculation.
