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This case-control study examined the potential for a common etiology of Parkinson's disease (PD) and Alzheimer's disease (AD) using reported family history. Structured interviews were used to collect AD and PD family history from subjects (n = 1,531) with AD, PD, AD/PD, or controls. Intergroup analysis compared reported AD and PD family histories in the three case groups to the histories reported in the control group. Intragroup analysis stratified each diagnostic group based on positive family history of AD, then compared the subgroups for a family history of PD. Subjects with AD had a higher risk of having a family history of AD [odds ratio (OR) 2.3; 1.5-3.4] and subjects with PD had a higher risk of having a family history of PD (OR 2.2; 1.2-4.0) as compared to control subjects. Intergroup analyses revealed no significant crossed risk, increased risk of subjects with AD having a family history of PD vs controls and vice versa. Intragroup analysis found that subjects with PD and a family history of AD were more likely to have a family history of PD (OR 1.7; 1.1-2.6) when compared to subjects with PD and no family history of AD. A similar trend was found for subjects with AD (OR 1.7; 0.9-3.1). AD and PD cases each have an increased familial risk of their respective disease. Probands with AD or PD and a family history of either disease have a higher crossed risk of a family history of the other disease. These findings suggest the existence of common genetic and/or environmental factors that predispose to both AD and PD in the subset of cases with positive family history of both neurodegenerative diseases.