Affiliations: [a] Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria), Murcia, Spain | [b] Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain | [c] Murcia Brain Bank, Murcia, Spain | [d] Department of Neuropathology and Brain Tissue Bank, Fundación CIEN, Carlos III Health Institute, Madrid, Spain
Correspondence:
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Correspondence to: Juan Marín-Muñoz, MD, Dementia Care Unit, Virgen de la Arrixaca University Hospital, IMIB (Instituto Murciano de Investigación Biosanitaria) Murcia, Carretera Madrid-Cartagena s/n, CP 30120 El Palmar, Murcia, Spain. Tel.: +34 9 6836 9409; Fax: +34 9 6836 9408; E-mail: juanmarinisla@gmail.com.
Abstract: Mutations in the presenilin 2 gene (PS2) are an extremely rare cause of early-onset autosomal dominant Alzheimer’s disease (AD), accounting for only 5% of these families. These cases represent a particular model of AD, and the scarcity of reports on their clinical phenotypes makes them of great interest. We report a family with early-onset autosomal dominant AD in four members, where the two living siblings were found to carry the novel PS2 mutation Gly212Val (exon 7, transmembrane domain IV) with highly predicted pathogenicity. Age at onset ranged from 60 to 65 years and three of the cases died between ages 74 and 76 years. Clinical phenotype was quite homogeneous among affected members of the family, and overall features, including cognitive decline, tau/p-tau and amyloid-β cerebrospinal fluid markers, neuroimaging, and neuropathology were consistent with typical AD. Lewy bodies were present but restricted to the amygdala.
