Affiliations: [a] Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan | [b] Department of Neurology, Shin-Kong WHS Memorial Hospital, Taipei, Taiwan | [c] Department of Pathology and Laboratory Medicine, Shin-Kong WHS Memorial Hospital, Taipei, Taiwan | [d] Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan | [e] Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan | [f] Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
Correspondence:
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Correspondence to: Jung-Lung Hsu, MD, Department of Neurology, Shin-Kong WHS Memorial Hospital, 95 Wen-Chang Road, 111 Taipei, Taiwan. Tel.: +886 2 28332211, ext 2598; Fax: +886 2 28344906; E-mail: [email protected].
Abstract: Familial Alzheimer's disease (FAD) is genetically heterogeneous, autosomal dominant, with nearly 100% penetrance. In FAD, most common causative genetic mutations are presenilin 1 (PSEN1), presenilin 2 and amyloid-β protein precursor. We demonstrate a family presenting as early-onset AD with a rapid deterioration course and seizure developed after 1.5 years of symptoms. A histopathological examination of the frontal cortex showed amyloid deposition and abundant phosphorylated tau deposition. In both cases, a single nucleotide mutation from guanine to adenine at exon 7 was found in PSEN1 (c.617G>A, codon change from GGT to GAT). Though G206D mutation in PSEN1 gene was found in FAD, no clinical phenotype or pathological finding was documented. This is the first report of PSEN1 mutation (Gly206Asp) with features of seizure and a rapid progressive cognitive decline in a pathologically confirmed case of FAD.
Keywords: Alzheimer's disease, amyloid-β protein precursor, epilepsy, presenilin 1 (PSEN1), tau protein
