The effects of apolipoprotein E genotype, α‐synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology

Bar, Roni; Boehm‐Cagan, Anat; Luz, Ishai; Kleper‐Wall, Yarden; Michaelson, Daniel M.

doi:10.1016/j.dadm.2017.08.003

Cited by 13

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

The effects of apolipoprotein E genotype, α‐synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology

Bar, Roni, Boehm‐Cagan, Anat, Luz, Ishai, Kleper‐Wall, Yarden, Michaelson, Daniel M.·2018·Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

DOI 10.1016/j.dadm.2017.08.003PMC PMC5678739

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Abstract

Introduction: Alzheimer's disease (AD) and synucleinopathies share common pathological mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α‐synuclein deficiency (α‐syn−/−) and sex on apoE4‐driven pathologies. Methods: AD‐related, synaptic, and vascular markers were analyzed in female and male α‐syn−/− and α‐syn+/+ apoE4, apoE3, and apoE3/E4 mice. Results: ApoE4 was hypolipidated, and this effect was unchanged by α‐syn−/− and sex. The levels of synaptic markers were lower, and the levels of AD‐related parameters were higher in female α‐syn−/− apoE4 mice compared with the corresponding apoE3 mice. By comparison, apoE4 had small effects on the AD parameters of male and female α‐syn+/+ apoE4 mice. Discussion: Although α‐syn−/− does not affect the upstream lipidation impairment of apoE4, it acts as a “second hit” enhancer of the subsequent apoE4‐driven pathologies.

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ApoE4-lipoproteins are poorly lipidated compared to apoE3-lipoproteins.
“apoE4-lipoproteins are poorly lipidated compared to apoE3-lipoproteins.”
From Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation (2023) · cites this paper as [20]

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Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits
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MethodSelf-citation
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APOE and Alzheimer’s Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer’s Pathogenesis
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Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation
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Authors: Bar, R., Boehm‐Cagan, A., Luz, I., Kleper‐Wall, Y., & Michaelson, D. M.
Affiliations: Department of Neurobiology, George S. Wise Faculty of Life Sciences Sagol School of Neuroscience, Tel Aviv University Tel Aviv Israel
Venue: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Publisher: Wiley
Published: 2017-09-06
Volume: 10
Issue: 1
Pages: 1-11
ISSN: 2352-8729
DOI: 10.1016/j.dadm.2017.08.003
PMC: PMC5678739
Cited by: 13
References: 11
Language: en
Licence: creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders: Legacy Heritage Bio-Medical Program of the Israel Science Foundation (1575/14)
Sagol Foundation

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The effects of apolipoprotein E genotype, α‐synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology

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