Recent trials in Alzheimer's disease (AD) demonstrate encouraging outcomes. These trials target risk mechanisms identified through genetic analysis whilst directly aiming to reduce progression rates. Show more
Recent trials in Alzheimer's disease (AD) demonstrate encouraging outcomes. These trials target risk mechanisms identified through genetic analysis whilst directly aiming to reduce progression rates. Evidence from other neurodegenerative diseases suggests the genetics of progression is distinct from risk of disease. To expand these initial successes and improve clinical outcomes further we need to understand genetics of progression of disease. These can be deduced through rigorous analysis of meticulously phenotyped longitudinal cohorts. In this study we first looked at known genetic drivers of risk, namely polygenic risk scores for AD and A total of 387 individuals with, genetic data, amyloid positivity and in active decline (ADNI (n=222) and AIBL(n=165)) were used to perform generalised mixed effects linear model genome wide association studies of longitudinal cognitive decline as measured by mini mental state examination. The resulting summary statistics were subjected z, and colocalization analyses. Established AD risk factors, including These findings enhance our understanding of the biological underpinnings of AD progression, opening new avenues for therapeutic intervention. Show less