P4‐124: An examination of previously reported Alzheimer candidate genes within a large genome‐wide association dataset

homogeneous. Clinical phenotype was a progressive cognitive decline in all cases, often with depression and apathy in early stages. Distinct features associated with specific mutations included: His163Arg, prominent behavioral syndrome with visual hallucinations, disruptive behavior, apathy, and motor stereotypes; Val261Leu, spastic paraparesis and dystonia; Val272Ala, subcortical profile of cognitive deterioration with depression, apathy and parkinsonism. Autopsy in one case with this latter mutation showed cortical and subcortical Lewy bodies, besides definitive AD. Leu282Arg, myoclonus and seizures. Duration of the disease to death was about a decade, similar for all mutations. Conclusions: This series expands the clinical phenotype of early onset AD associated with PSEN1 mutations, which is more prone to associate atypical features than late onset AD, and adds two novel mutations to the AD mutations spectrum.