Atypical dementia associated with a novel presenilin-2 mutation

We describe an Italian pedigree with hereditary dementia associated with a novel T122R mutation in the presenilin-2 gene (PSEN2). The clinical history, symptom presentation, and structural neuroimaging were consistent with an atypical form of dementia. Disease expression varied within family members. One in a pair of mutated monozygotic twins had evident signs of disease, whereas the other did not, even if her functional neuroimaging investigations, cerebrospinal fluid levels of Aβ1-42, and Tau protein were able to provide markers for future disease development. These observations suggest the importance of still unknown biological and perhaps environmental factors in the disease determination.