Science subjournal: it is revealed that apoE4 aggravates α - synuclein lesions, and this aggravation is not related to amyloid protein

February 26, 2020 / BIOON / - -- scientists have identified several genetic risk factors for neurodegenerative diseases Among these genetic risk factors, APOE ε 4 allele (apoE4) is the strongest genetic risk factor for tardive Alzheimer's disease, which is mainly caused by driving amyloid β pathology Recently, apoE4 has also been found to be a genetic risk factor for Lewy body dementia (LBD) How apoE4 drives the risk of dementia in Lewy body and whether it has a direct effect on α - synuclein pathology is unclear In a new study, researchers from Mayo Clinic in the United States studied whether apoE4 affects α - synuclein pathology in mouse models and Parkinson's disease patients The related research results were recently published in the Journal of Science Translational Medicine The title of the paper is "apoE4 exacerbates α - synuclein pathway and related toxicity independent of aminoid" In the substantia nigra area of the brain of Parkinson's disease patients, immunohistochemical analysis of α - synuclein showed a positive staining (brown) of the Lewisite in the nerve, with pictures from Wikipedia Adeno-associated virus (AAV) was used to deliver α - synuclein gene in apoe2, apoE3 or apoE4 expressing human apoE targeted replacement mice, and a mouse model of synuclein disease (synuclein disease) was developed They found that at 9 months of age, apoE4, not apoe2 or apoE3, increased α - synuclein pathology, impaired behavior, increased neuronal and synaptic loss, and increased astrocytosis In the mouse model of synuclein disease, apoE4 exacerbated α - synuclein pathology without amyloid They also observed an increase in α - synuclein pathology in apoE4 in the brains of people with minimal amyloid pathology in Lewy's dementia Transcriptome analysis in apoE4 expressing synuclein disease mice highlighted changes in lipid and energy metabolism and synaptic related pathways These data confirm that apoE4 plays a pathogenic role in aggravating the pathology of α - synuclein, and this role has nothing to do with amyloid protein, which provides new insights on how apoE4 can increase the risk of dementia in Lewy body (bio Com) reference: Na Zhao et al ApoE4 exacerbates α - synuclein pathway and related toxicity independent of aminoid Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aay1809