TY - JOUR
T1 - Apolipoprotein E in Alzheimer's disease and other neurological disorders
AU - Verghese, Philip B.
AU - Castellano, Joseph M.
AU - Holtzman, David M.
N1 - Funding Information:
DMH is a paid member of the scientific advisory boards of En Vivo and Satori and has received payments from C2N Diagnostics as a scientific adviser and royalties from a Washington University patent licensed to C2N Diagnostics. DMH's laboratory at Washington University receives research support grants from Eli Lilly, AstraZeneca, and Pfizer. The other authors declare no conflicts of interest.
Funding Information:
PBV is supported by an American Health Assistance postdoctoral fellowship ( AHAF 3857–43287 ). JMC is supported by a US National Institutes of Health (NIH) F31 predoctoral fellowship ( AG034004 ). DMH is supported by NIH grants AG13956, AG03991, AG026276 , and NS034467 .
PY - 2011/3
Y1 - 2011/3
N2 - Apolipoprotein E (APOE) is a 299-aminoacid protein encoded by the APOE gene. Three common polymorphisms in the APOE gene, e{open}2, e{open}3, and e{open}4, result in a single aminoacid change in the APOE protein. APOE e{open}2, e{open}3, and e{open}4 alleles strongly alter, in a dose-dependent manner, the likelihood of developing Alzheimer's disease and cerebral amyloid angiopathy. In particular, APOE e{open}4 is associated with increased risk for Alzheimer's disease whereas APOE e{open}2 is associated with decreased risk. The effects of APOE genotype on risk of these diseases are likely to be mediated by differential effects of APOE on amyloid-β accumulation in the brain and its vasculature. Response to treatment for Alzheimer's disease might differ according to APOE genotype. Because convincing evidence ties the APOE genotype to risk of Alzheimer's disease and cerebral amyloid angiopathy, APOE has been studied in other neurological diseases. APOE e{open}4 is associated with poor outcome after traumatic brain injury and brain haemorrhage, although the mechanisms underlying these associations are unclear. The possibility that APOE has a role in these and other neurological diseases has been of great interest, but convincing associations have not yet emerged.
AB - Apolipoprotein E (APOE) is a 299-aminoacid protein encoded by the APOE gene. Three common polymorphisms in the APOE gene, e{open}2, e{open}3, and e{open}4, result in a single aminoacid change in the APOE protein. APOE e{open}2, e{open}3, and e{open}4 alleles strongly alter, in a dose-dependent manner, the likelihood of developing Alzheimer's disease and cerebral amyloid angiopathy. In particular, APOE e{open}4 is associated with increased risk for Alzheimer's disease whereas APOE e{open}2 is associated with decreased risk. The effects of APOE genotype on risk of these diseases are likely to be mediated by differential effects of APOE on amyloid-β accumulation in the brain and its vasculature. Response to treatment for Alzheimer's disease might differ according to APOE genotype. Because convincing evidence ties the APOE genotype to risk of Alzheimer's disease and cerebral amyloid angiopathy, APOE has been studied in other neurological diseases. APOE e{open}4 is associated with poor outcome after traumatic brain injury and brain haemorrhage, although the mechanisms underlying these associations are unclear. The possibility that APOE has a role in these and other neurological diseases has been of great interest, but convincing associations have not yet emerged.
UR - http://www.scopus.com/inward/record.url?scp=79951713725&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(10)70325-2
DO - 10.1016/S1474-4422(10)70325-2
M3 - Review article
C2 - 21349439
AN - SCOPUS:79951713725
SN - 1474-4422
VL - 10
SP - 241
EP - 252
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 3
ER -