TY - JOUR
T1 - ApoE and Aβ in Alzheimer's disease
T2 - Accidental encounters or partners?
AU - Kanekiyo, Takahisa
AU - Xu, Huaxi
AU - Bu, Guojun
N1 - Funding Information:
This work was supported by NIH grants R01AG035355, R01AG027924, R01AG046205, P01AG030128, P01NS074969, an Alzheimer’s Association IIRG, and a Cure Alzheimer’s Fund (to G.B.) and Mayo Clinic CRM Career Developmental Award and an Alzheimer’s Association NIRG (to T.K.). We thank Caroline T. Stetler, Melissa C. Wren, and Caroline S. Casey for careful readings of this manuscript.
PY - 2014/2/19
Y1 - 2014/2/19
N2 - Among the three human apolipoprotein E (apoE) isoforms, apoE4 increases the risk of Alzheimer's disease (AD). While transporting cholesterol is a primary function, apoE also regulates amyloid-β (Aβ) metabolism, aggregation, and deposition. Although earlier work suggests that different affinities of apoE isoforms to Aβ might account for their effects on Aβ clearance, recent studies indicate that apoE also competes with Aβ for cellular uptake through apoE receptors. Thus, several factors probably determine the variable effects apoE has on Aβ. In this Review, we examine biochemical, structural, and functional studies and propose testable models that address the complex mechanisms underlying apoE-Aβ interaction and how apoE4 may increase AD risk and also serve as a target pathway for therapy.
AB - Among the three human apolipoprotein E (apoE) isoforms, apoE4 increases the risk of Alzheimer's disease (AD). While transporting cholesterol is a primary function, apoE also regulates amyloid-β (Aβ) metabolism, aggregation, and deposition. Although earlier work suggests that different affinities of apoE isoforms to Aβ might account for their effects on Aβ clearance, recent studies indicate that apoE also competes with Aβ for cellular uptake through apoE receptors. Thus, several factors probably determine the variable effects apoE has on Aβ. In this Review, we examine biochemical, structural, and functional studies and propose testable models that address the complex mechanisms underlying apoE-Aβ interaction and how apoE4 may increase AD risk and also serve as a target pathway for therapy.
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U2 - 10.1016/j.neuron.2014.01.045
DO - 10.1016/j.neuron.2014.01.045
M3 - Review article
C2 - 24559670
AN - SCOPUS:84896726518
SN - 0896-6273
VL - 81
SP - 740
EP - 754
JO - Neuron
JF - Neuron
IS - 4
ER -