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Apolipoprotein E isoforms in Alzheimer's disease pathology and etiology
Author(s) -
Baum Larry,
Chen Lan,
Ng HoKeung,
Pang Chi Pui
Publication year - 2000
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/1097-0029(20000815)50:4<278::aid-jemt5>3.0.co;2-t
Subject(s) - apolipoprotein e , neurite , senile plaques , amyloid (mycology) , alzheimer's disease , knockout mouse , genetically modified mouse , pathology , degenerative disease , neuroscience , biology , transgene , medicine , disease , in vitro , receptor , gene , biochemistry
The apolipoprotein E (apoE) ϵ4 allele increases risk of Alzheimer's disease (AD), perhaps by accelerating plaque formation, or by impairing neuron repair. Considerable evidence supports both mechanisms. AD patients with ϵ4 have more and earlier amyloid deposits than do patients without ϵ4. The same is true of non‐demented control subjects. In vitro, all apoE isoforms inhibit amyloid β protein (Aβ) aggregation, but apoE4 less effectively than apoE3. Transgenic amyloid‐producing mice expressing apoE3 or apoE4 develop less Aβ deposition than apoE knockout mice. These observations are consistent with an effect of apoE isoforms on Aβ aggregation in AD. ApoE is important for neurite maintenance since apoE knockout mice lose neurites and suffer behavioral deficits with aging or treatment with excitotoxins. ApoE4 mice show similar defects, but apoE3 mice are normal. AD patients with ϵ4 show more neuritic deficits than ϵ3 carriers. ApoE ϵ4 also worsens neurological impairment in head injury, stroke, and multiple sclerosis. Thus, apoE4 is less effective at neurite maintenance. Perhaps ϵ4 increases AD risk by both mechanisms: allowing amyloid deposition and failing to repair neurites. In either case, introducing apoE3 or apoE2 into the brain, for example by gene therapy or cell grafts, might delay AD progression. Microsc. Res. Tech. 50:278–281, 2000. © 2000 Wiley‐Liss, Inc.