Presenilin 1 Gene Mutation (M139V) in a German Family with Early-Onset Alzheimer's Disease: A Case Report.

Objective This study describes a 44-year-old German male with early-onset Alzheimer's disease as a result of a M139V presenilin 1 mutation. The patient has at least seven affected family members, spanning at least four generations. Method We performed a complete demographic, genetic, neuropsychological, neuropsychiatric, neuroradiological, and neuropathological characterizations of this patient. The findings were compared with previous reports of patients with the same mutation. Demographic, neuropsychological, neuropsychiatric, neuroradiological, and neuropathological data from several affected members of the patient's family were also addressed. Results We describe similarities shared with other cases, including age at onset, rapid disease progression, severe deficits in arithmetic and visuo-constructive abilities with relative preservation of naming skills, and the presence of predominant frontal behavioral symptoms. Differences with respect to previously described cases, including the absence of positive neurological or radiological findings, psychotic symptoms, or a depressive disorder, are also identified and discussed. Conclusions Heterogeneity in symptoms between affected patients from the same or from different families suggests that individual, genetic, or epigenetic factors most likely modulate the phenotype of patients carrying the M139V mutation.