Clinical and post-mortem data from the Memory and Aging Project offer an unprecedented opportunity to investigate biologic pathways linking risk factors to clinical disease among a socioeconomically diverse cohort of older men and women. This investigation involves first understanding the relation of pathological indices to clinical AD and MCI. We found that AD pathology with other common pathologies, in particular cerebrovascular disease and Lewy bodies, are the most common cause of clinically probable AD and a common cause of MCI and amnestic MCI. These data are consistent with and extend findings from several other clinical-pathologic studies [214–224]. The findings raise the possibility that some risk factors for clinical AD are likely to be risk factors for pathologies other than AD. For example, APOE is strongly related to AD pathology and CR1 and CEPT less so. Thus, these polymorphisms appear to be related to AD in part through an association with AD pathology. Understanding the mechanism linking these polymorphisms to amyloid deposition would be a useful for developing strategies for interventions. By contrast, several other risk factors for clinical AD were not directly related to measures of AD pathology. Thus, they must work through an alternate pathway.
