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Lookup NU author(s): Dr Clive Ballard, Emeritus Professor Robert Perry, Dr Christopher Morris
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Most cases of familial presenile Alzheimer's disease are caused by mutations in the presenilin-1 (PSEN-1) gene, most of these mutations being missense mutations. A mutation in the splice donor site of intron 4 of PSEN-1 has been described recently which results in aberrant splicing of PSEN-1 mRNA, causing insertion of an additional amino acid, Thr113-114ins, into the protein. We studied the neuropathology of four cases bearing this mutation in an attempt to clarify the pathology of this hereditary form of Alzheimer's disease and to determine whether it differs from other familial forms of the disease. The disease presented as a progressive cognitive decline, myoclonus and seizures developing later in the disease, a feature common to PSEN-linked Alzheimer's disease. The course of the disease was relatively rapid, death occurring approximately 6 years after onset, Pathology in the intron 4 cases demonstrated a severe Alzheimer's disease pathology with abundant deposition of beta -amyloid (A beta) 1-42 senile plaques and the formation of neurofibrillary tangles. Amyloid angiopathy was present in these cases and was readily demonstrated by A beta 1-40 staining, particularly in the cerebellum. Cases with the intron 4 mutation appear clinically and pathologically similar to other cases of early-onset Alzheimer's disease bearing PSEN-1 mutations.
Author(s): Perry RH; Morris CM; Ballard CG; Singleton AB; Hall R; Xuereb JH; Rubinsztein DC; Tysoe C; Matthews P; Cordell B; Kumar-Singh S; De Jonghe C; Cruts M; van Broeckhoven C
Publication type: Article
Publication status: Published
Journal: Brain
Year: 2000
Volume: 123
Issue: 12
Pages: 2467-2474
ISSN (print): 0006-8950
ISSN (electronic): 1460-2156
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/brain/123.12.2467
DOI: 10.1093/brain/123.12.2467
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