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The purpose of this study was to infer causal relationships between 22 previously reported risk factors for Alzheimer's disease (AD) and the "AD phenome" AD, AD age of onset (AAOS), hippocampal volume, cortical surface area and thickness, cerebrospinal fluid (CSF) levels of amyloid-β (Aβ ), tau, and ptau , and the neuropathological burden of neuritic plaques, neurofibrillary tangles (NFTs), and vascular brain injury (VBI). Polygenic risk scores (PRS) for the 22 risk factors were computed in 26,431 AD cases/controls and the association w