Three novel presenilin 1 mutations marking the wide spectrum of age at onset and clinical patterns in familial Alzheimer’s disease

Presenilin 1 (PSEN1) mutations are the major cause of autosomal dominant Alzheimer’s disease (ADAD). Here we report three novel PSEN1 mutations: Ile238_Lys239insIle, Ala246Pro and Ala164Val from patients who manifested in their twenties, forties and seventies, respectively, with variant clinical presentations of dementia. These cases exemplify the tremendous heterogeneity of clinical phenotypes and age of onset associated with PSEN1 mutations. The possibility of ADAD—not previously suspected in two of our patients—should always be considered in neurodegenerative conditions albeit they might neither exhibit the typical clinical picture of Alzheimer’s disease nor early onset dementia, which is regarded the primary clinical sign of hereditary neurodegeneration.