The effects of apolipoprotein E genotype, α‐synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology
| Autor: | Anat Boehm-Cagan, Ishai Luz, Yarden Kleper-Wall, Roni Bar, Daniel M. Michaelson |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Pathology medicine.medical_specialty animal diseases Disease Biology lcsh:Geriatrics Apolipoprotein E4 (apoE4) apoE‐targeted replacement mice lcsh:RC346-429 03 medical and health sciences 0302 clinical medicine apoE-targeted replacement mice mental disorders Genetics medicine Dementia Apolipoprotein e4 Enhancer Pathological lcsh:Neurology. Diseases of the nervous system Synucleinopathies α-Synuclein deficiency Alzheimer's disease medicine.disease α‐Synuclein deficiency Psychiatry and Mental health lcsh:RC952-954.6 030104 developmental biology nervous system α synuclein lipids (amino acids peptides and proteins) Sex Neurology (clinical) human activities 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol 10, Iss 1, Pp 1-11 (2018) Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring |
| ISSN: | 2352-8729 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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