Frontotemporal Dementia-like Phenotypes Associated With Presenilin-1 Mutations

Frontal behavioral changes may be the presenting features of single-photon emission tomography (presenilin-1 [PS-1]) mutations, the most common cause of familial Alzheimer's disease (AD). The authors describe a PS-1 (M233L) mutation with the features of frontotemporal dementia (FTD) and review the literature. PS-1 mutations may produce FTD-like phenotypes with the neuropathology of AD. Some PS-1 mutations have additional Pick's bodies, a neuropathological marker of FTD, and a report of a PS-1 (G183V) mutation found Pick's bodies without amyloid plaques. The patient and the literature suggest that PS-1 mutations result in an overlapping continuum of the clinical and neuropathological features of AD and FTD. In PS-1 mutations, the expression of AD or FTD may depend on the degree of loss of function of the PS-1 gene and the resultant τ pathophysiology.