Genetic Associations with Alzheimer's, Lewy Body and Vascular Neuropathology Reveal Shared and Distinct Biological Pathways

INTRODUCTION: Alzheimers, Lewy body and vascular neuropathology underpin the most common forms of dementia. Large-scale genetic studies tend to rely on clinical diagnoses and therefore may be subject to misdiagnoses and co-neuropathologies that occur. METHODS: Utilising the extension neuropathology data available on the Brains for Dementia Research cohort, this study performed whole-genome association analyses based on common neuropathology present in dementia. Genetic data was generated on the Illumina Neurobooster array and analysed using standard analyses pipelines in PLINK. RESULTS: Several associations were observed in and around the APOE locus but only in relation Alzheimers neuropathology. Whilst there was a convergence of common gene associations across the different neuropathology groups, there were distinct associations of individual SNPs. DISCUSSION: Different neuropathological outcomes appear to be driven by distinct genetic variants but converge on shared genes and biological processes related to neuronal structure and communication. Understanding these common pathways may provide new insights into mechanisms underlying mixed neuropathology and age-related neurodegeneration.