Science: apoE4 variants make Parkinson's patients more likely to develop dementia

February 10, 2020 / Biovalley BIOON / - -- Parkinson's disease is a progressive nervous system disease characterized by tremor, rigidity, slow movement and impaired balance Dementia is one of the most serious consequences of Parkinson's disease Eighty percent of Parkinson's patients developed dementia within 20 years of diagnosis, and those with specific variants of ApoE gene were at a particularly high risk In a new study, researchers from the University of Washington in the United States found clues about the link between Parkinson's disease, ApoE and dementia They found that harmful Parkinson's disease proteins spread more quickly in the brains of mice with a high-risk variant of apoE, while the memory and thinking abilities of Parkinson's patients with this variant declined more quickly These findings may lead to apoE targeted therapies to slow or prevent cognitive decline in patients with Parkinson's disease Relevant research results were published in the Journal of Science Translational Medicine on February 5, 2020 The title of the paper is "apoE genetype regulations pathway and disease progress in syncleinopathy" Picture from Science Translational Medicine, 2020, DOI: 10.1126/scitranslmed.aay3069 Dr Albert Davis, the first author of the paper and assistant professor of Neuroscience at the University of Washington, said, "dementia has caused great losses to Parkinson's patients and their caregivers Dementia usually determines whether Parkinson's patients can stay at home or must go to a sanatorium " In the United States, an estimated 930000 people suffer from Parkinson's disease The disease is thought to be caused by a toxic clump of a protein called alpha synuclein This protein builds up in the part of the brain that is responsible for movement This can cause brain cells to damage and kill them After many years of motor symptoms, cognitive problems will appear These protein aggregates associated with exercise problems are also associated with dementia, but how this happens is unclear Davis and his colleagues, including Dr David Holtzman, co-author of the paper, observed clues to the risk of apoE An apoE variant called apoE4 increases the risk of Alzheimer's disease by three to five times Like Parkinson's disease, Alzheimer's disease is a neurodegenerative disease caused by the spread of toxic protein aggregates throughout the brain, although some proteins involved in this disease are different ApoE4 increases the risk of Alzheimer's disease dementia, in part because it stimulates the aggregation of Alzheimer's disease proteins, leading to brain damage The researchers speculate that apoE4 also triggers the growth of toxic aggregates of Parkinson's disease proteins After studying mice with alpha synuclein forms that are prone to form protein clumps, Davis, Holtzman, and colleagues genetically engineered these mice to carry one of the human apoE variants, apoe2, apoE3, or apoE4, or to have no apoE at all These researchers found that apoE4 mice (i.e mice carrying apoE4) had more α - synuclein aggregates than apoE3 mice or apoe2 mice Further experiments showed that these protein masses also spread more widely in apoE4 mice In summary, these findings suggest that apoE4 is directly involved in the deterioration of symptoms of brain disease in these mice "What really stands out is that apoe2 mice are less affected than other mice," Davis said It may actually have a protective effect, which we are studying If we do find apoe2 to be protective, we may be able to use this information to design therapies to reduce the risk of dementia " To study the effect of apoE variants on dementia in Parkinson's patients, the researchers analyzed open data from three groups of Parkinson's patients They tracked two patient cohorts - one from the Parkinson's progress markers initiative, with 251 patients, and the other from the Washington University movement disorders center, with 170 patients - for years In both cohorts, cognitive decline was faster in patients with apoE4 than in patients with apoE3 People with two copies of apoe2 were rare, but none of the three patients with two copies of apoe2 showed any cognitive decline during the study The third cohort, from the neurogenetics research consortium, consisted of 1030 Parkinson's patients whose cognitive abilities were assessed only once The researchers found that apoE4 patients in this cohort had cognitive problems at a younger age and had more severe cognitive deficits at the time of their assessment than patients with apoE3 or apoe2 "Parkinson's disease is more common, but there are other rare diseases that are also caused by alpha synuclein aggregation and have very limited therapeutic options," Davis said Targeting apoE with drugs may be a way to change the course of such diseases " ApoE does not affect the overall risk of Parkinson's disease or the rate of deterioration of motor symptoms Therefore, targeted therapy of apoE may avoid dementia without affecting other symptoms Even so, Davis said, it could be beneficial "Once people with Parkinson's have dementia, the financial and emotional costs for them and their families will be huge," Davis said If we can reduce their risk of dementia, then we can significantly improve their quality of life " (BIOON Com) reference: 1 Albert A Davis et al APOE genotype regulations pathway and disease progress in syncleinopathy Science Translational Medicine, 2020, doi:10.1126/scitranslmed.aay3069 2.Gene ID'd as potential therapeutic target for dementia in Parkinson's https://medicalxpress.com/news/2020-02-gene-idd-potential-therapeutic-dementia.html