Alzheimer Disease–like Phenotype Associated With the c.154delA Mutation in Progranulin

Abstract

Alzheimer disease (AD) is pathologically characterized by neurofibrillary tangles and neuritic plaques. The hallmark of the cognitive profile is prominent early memory disturbance, in distinct contrast to frontotemporal lobar degenerations (FTLDs), in which pathologic FTLD is usually associated with prominent early executive, behavioral, or language disturbances typical of frontotemporal dementia with (FTDP) or without parkinsonism. Several kindreds with FTDP associated with FTLD with ubiquitin-positive inclusions (FTLD-U) pathologic abnormalities and with mutations in the gene encoding progranulin (PGRN; OMIM *138945) were recently described.^1-4 Subsequently published clinical phenotypes have included FTDP, primary progressive aphasia, corticobasal syndrome, and progressive supranuclear palsy.⁵ This article presents a detailed description of a large kindred in which several individuals followed a clinical course typical of AD associated with a mutation in PGRN and underlying FTLD-U pathologic abnormalities. These findings extend the clinical phenotypes and magnetic resonance imaging (MRI) findings associated with mutations in PGRN with the pathologic substrate of FTLD-U.