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Pathology of early-onset Alzheimer's disease cases bearing the Thr113-114ins presenilin-1 mutation

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.

Publication metadata

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


DOI: 10.1093/brain/123.12.2467


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