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Title
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APOE epsilon 2 is associated with increased tau pathology in primary tauopathy
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Author
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Abstract
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| Apolipoprotein E (APOE) epsilon 4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease mainly by modulating amyloid-beta pathology. APOE epsilon 4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE epsilon 2/epsilon 2. We also show that in humans, the APOE epsilon 2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE epsilon 2/epsilon 2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE epsilon 2 status may influence the risk and progression of tauopathy. |
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Language
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English
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Source (journal)
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Nature communications
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Publication
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2018
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ISSN
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2041-1723
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DOI
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10.1038/S41467-018-06783-0
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Volume/pages
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9
(2018)
, 11 p.
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Article Reference
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4388
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ISI
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000447841800001
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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