A Novel Mutation in the Predicted TMIII Domain of the PSEN2 Gene in an Italian Pedigree with Atypical Alzheimer's Disease

Article type: Short Communication

Authors: Piscopo, Paola^a | Talarico, Giuseppina^b | Crestini, Alessio^a | Gasparini, Marina^b | Malvezzi-Campeggi, Lorenzo^a | Piacentini, Elisa^a | Lenzi, Gian Luigi^b | Bruno, Giuseppe^b | Confaloni, Annamaria^{a; *}

Affiliations: [a] Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy | [b] Department of Neurological Sciences, Memory Clinic, University of Rome “Sapienza”, Rome, Italy

Correspondence: [*] Correspondence to: Dr. Annamaria Confaloni, PhD, Department of Cell Biology and Neurosciences, Section of Clinics, Diagnosis and Therapy of Central Nervous System Diseases, Istituto Superiore di Sanita', Viale Regina Elena, 299, 00161 Rome, Italy. Tel.: +39 06 49902930; Fax: +39 6 4938 7143; E-mail: annamaria.confaloni@iss.it.

Note: [] Handling Associate Editor: Amalia Bruni

Abstract: Alzheimer's disease (AD) is characterized by accumulation of toxic amyloid-β (Aβ) in the brain, with neuronal death, and an associated increased Aβ42/40 ratio. Several mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid-β precursor protein are involved in the etiology of familial AD (FAD); these mutations alter the Aβ42/40 ratio and promote apoptosis. We describe an Italian pedigree linked to a novel mutation (S175C) at the third transmembrane domain of PSEN2. Clinical phenotype in these individuals is characterized by fast cognitive decline with progressive memory impairment, early involvement of executive functions, behavioral disturbances, and extrapyramidal signs.

Keywords: Atypical dementia, behavioral disturbances, genetics, mutation, presenilins

DOI: 10.3233/JAD-2010-1369

Journal: Journal of Alzheimer's Disease, vol. 20, no. 1, pp. 43-47, 2010