P1-348: Early onset familial Alzheimer’s disease: First Portuguese cases

Abstract

Autosomal dominant early onset Alzheimer's disease (ADEOAD) is a rare form of disease, affecting less than 1% of AD cases and is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes have been reported. Recently we identified two previous reported mutations in presenilin 1 at chromosome 14 in two patients/families with very early onset AD. To present the first cases identified in Portugal. Description. Case 1 – Male with very early onset (35years) and fast progression. He presented an atypical clinical profile: cognitive and behavioral manifestations suggesting Frontotemporal dementia, extrapyramidal features, mainly dystonia, and family history of psychopathology but no dementia. Cerebral biopsy confirmed the diagnosis of AD. The previously reported mutation PS1 Met233Thr ATG>ACG(nt946) (Kwok JB, 1997) was identified by sequence analysis and mutation scanning. Case 2 – Female with very early onset (35years) and typical AD with autosomal dominant family history. The diagnosis was confirmed by necropsy study in her mother. Sequence analysis and mutation scanning revealed the previous described PS1 Ala260Thr GCT>GTT(nt1027) (Rogaev EI, 1995). We present the first two cases/families of autosomal dominant early onset Alzheimer's disease (ADEOAD) described in Portugal. One of the cases presents a clinical picture not previously described in PSEN1 mutations.