TY - JOUR
T1 - The Role of Apolipoprotein E in Alzheimer's Disease
AU - Kim, Jungsu
AU - Basak, Jacob M.
AU - Holtzman, David M.
N1 - Funding Information:
This work was supported by NIH grants AG13956 (D.M.H.) and grants from the American Health Assistance Foundation (D.M.H. and J.K.). We would like to thank Dr. John R. Cirrito for critical reading of the manuscript. The Holtzman lab receives a grant from Eli Lilly related to apoE.
PY - 2009/8/13
Y1 - 2009/8/13
N2 - The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Aβ aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE ε4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
AB - The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Aβ aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE ε4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
UR - http://www.scopus.com/inward/record.url?scp=68249134074&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2009.06.026
DO - 10.1016/j.neuron.2009.06.026
M3 - Review article
C2 - 19679070
AN - SCOPUS:68249134074
SN - 0896-6273
VL - 63
SP - 287
EP - 303
JO - Neuron
JF - Neuron
IS - 3
ER -