Assessment of genetic risk for improved clinical-neuropathological correlations
| Autor: | James B. Brewer, Barbara E. Spencer, Chun Chieh Fan, Robin G. Jennings |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Multifactorial Inheritance Aging Neurology Parkinson's disease Dementia with Lewy bodies Disease Neurodegenerative Bioinformatics Alzheimer's Disease lcsh:RC346-429 0302 clinical medicine Diagnosis 80 and over 2.1 Biological and endogenous factors Senile plaques Medical diagnosis Aetiology Aged 80 and over screening and diagnosis Parkinson Disease Detection Neurological Female Alzheimer’s disease Lewy Body Disease medicine.medical_specialty Lewy Body Dementia Clinical Sciences Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience Alzheimer Disease mental disorders medicine Acquired Cognitive Impairment Genetics Humans Genetic Predisposition to Disease Genetic Testing Pathological lcsh:Neurology. Diseases of the nervous system Aged business.industry Research Polygenic risk Prevention Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease Brain Disorders 4.1 Discovery and preclinical testing of markers and technologies 030104 developmental biology Parkinson’s disease Dementia Neurology (clinical) Biochemistry and Cell Biology business 030217 neurology & neurosurgery |
| Zdroj: | Acta neuropathologica communications, vol 8, iss 1 Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-10 (2020) Acta Neuropathologica Communications |
| Popis: | In the clinical diagnosis of dementia with Lewy bodies, distinction from Alzheimer’s disease is suboptimal and complicated by shared genetic risk factors and frequent co-pathology. In the present study we tested the ability of polygenic scores for Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease to differentiate individuals in a 2713-participant, pathologically defined sample. A dementia with Lewy bodies polygenic score that excluded apolipoprotein E due to its overlap with Alzheimer’s disease risk was specifically associated with at least limbic (transitional) Lewy-related pathology and a pathological diagnosis of dementia with Lewy bodies. An Alzheimer’s disease polygenic score was associated with neuritic plaques and neurofibrillary tangles but not Lewy-related pathology, and was most strongly associated with an Alzheimer’s pathological diagnosis. Our results indicate that an assessment of genetic risk may be useful to clinically distinguish between Alzheimer’s disease and dementia with Lewy bodies. Notably, we found no association with a Parkinson’s disease polygenic score, which aligns with evidence that dementia with Lewy bodies has a distinct genetic signature that can be exploited to improve clinical diagnoses. |
| Databáze: | OpenAIRE |
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