Challenging the boundaries: c9orf72 mutation presenting as Alzheimer's disease.

Abstract

C9orf72 hexanucleotide repeat expansion is a major cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), while its link with Alzheimer's disease (AD) is still unclear. We describe the case of a 53-year-old man with progressive memory and language deficits, mood disturbances, and a positive family history for ALS-FTD. Cerebrospinal fluid showed amyloid positivity, confirmed by amyloid-PET, with normal tau levels; [¹⁸F]FDG-PET revealed an AD-like temporoparietal hypometabolism. Genetic testing detected a pathogenic C9orf72 expansion, also present in his mother. This case suggests phenotypic heterogeneity of C9orf72-related disorders and a possible interplay with amyloid pathology.