title: Pathology of early-onset Alzheimer's disease cases bearing the Thr113-114ins presenilin-1 mutation.
abstract: 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-1-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 ss-amyloid (Ass) 1-42 senile plaques and the formation of neurofibrillary tangles. Amyloid angiopathy was present in these cases and was readily demonstrated by Ass 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.
authors: Medical Research Council Neurochemical Pathology Unit, Institute for the Health of the Elderly and Department of Neuropathology, Newcastle General Hospital, Newcastle upon Tyne, UK.
authors: A B
authors: AB
authors: Singleton
authors: R
authors: R
authors: Hall
authors: C G
authors: CG
authors: Ballard
authors: R H
authors: RH
authors: Perry
authors: J H
authors: JH
authors: Xuereb
authors: D C
authors: DC
authors: Rubinsztein
authors: C
authors: C
authors: Tysoe
authors: P
authors: P
authors: Matthews
authors: B
authors: B
authors: Cordell
authors: S
authors: S
authors: Kumar-Singh
authors: C
authors: C
authors: De Jonghe
authors: M
authors: M
authors: Cruts
authors: C
authors: C
authors: van Broeckhoven
authors: C M
authors: CM
authors: Morris
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D004569:Electroencephalography; D004739:England; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009207:Myoclonus / Q000209:etiology; D010375:Pedigree; D053764:Presenilin-1; D012640:Seizures / Q000209:etiology
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1