Research ArticleNEURODEGENERATIVE DISEASES

APOE genotype regulates pathology and disease progression in synucleinopathy

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Science Translational Medicine  05 Feb 2020:
Vol. 12, Issue 529, eaay3069
DOI: 10.1126/scitranslmed.aay3069

APOE4 beyond amyloid

Although several genetic risk factors for neurodegenerative disorders have been identified, often the mechanistic aspect is not clear. Now, Zhao et al. and Davis et al. investigated whether apolipoprotein E4 (APOE4) genotype, a major risk factor for neurodegenerative diseases, affected α-synuclein pathology in mouse models and Parkinson’s disease (PD) patients. Zhao et al. generated a mouse model of α-synucleinopathy and showed that APOE4 exacerbated α-synuclein pathology independent of amyloid. Davis et al. used mouse models of α-synucleinopathy and analyzed cognition in patients with PD to demonstrate that APOE4 directly regulated α-synuclein pathology and was associated with faster cognitive decline. These results provide insight into the mechanisms linking APOE genotype to neurodegenerative disorders.

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