Alzheimer's disease families with amyloid precursor protein mutations.

Details

Serval ID
serval:BIB_01A0ADD57F01
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Alzheimer's disease families with amyloid precursor protein mutations.
Journal
Annals of the New York Academy of Sciences
Author(s)
Rossor M.N., Newman S., Frackowiak R.S., Lantos P., Kennedy A.M.
ISSN
0077-8923 (Print)
ISSN-L
0077-8923
Publication state
Published
Issued date
1993
Volume
695
Pages
198-202
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; ReviewPublication Status: ppublish
Abstract
Early onset Familial Alzheimer's Disease (FAD) is an autosomal dominant disease with apparent complete penetrance. It is genetically heterogeneous with some families carrying mutations in the amyloid precursor protein (APP) gene which segregate with the disease. In addition, there is allelic heterogeneity with four mutations associated with FAD. Three mutations have been reported at APP 717, just distal to the C-terminus of the beta-amyloid domain, APP 717 val-ile, APP 717 val-phe, and APP 717 val-gly, which are associated with autopsy-proven Alzheimer's disease (AD). APP 670/671 lies at the N terminus of the beta-amyloid domain and is associated with clinically diagnosed FAD in two Swedish families. FAD tends to have prominent myoclonus and this is shared by the cases with APP mutations. In two unrelated UK families with APP 717 val-ile mutations there was early prominent memory impairment with dyscalculia proceeding to generalized cognitive impairment with a lack of insight. There was a late development of a gait disturbance with extrapyramidal features in some members. Positron emission tomography (PET) with fluorodeoxyglucose demonstrated posterior bitemporal biparietal hypometabolism in one case. Magnetic resonance imaging (MRI) showed generalized cerebral atrophy particularly affecting the temporal lobes and hippocampus. At autopsy, a single case showed extensive beta-amyloid deposition with congophilic angiopathy and widespread senile plaques and neurofibrillary tangles. The cytoskeletal pathology associated with abnormally phosphorylated tau was similar to cases of sporadic AD. In addition, there were widespread cortical and subcortical Lewy bodies. A single family with the APP 717 val-gly mutation also showed prominent myoclonus, lack of insight, and seizures, PET, in a single case, showed classical biparietal bitemporal hypometabolism. Autopsy, in a single case, showed diffuse deposits of beta-amyloid throughout the cortex with frequent neuritic plaques and neurofibrillary tangles. No other inclusion bodies were seen. There was severe congophilic angiopathy. The age at onset of APP mutations is around 50 years of age by contrast to other early onset FAD pedigrees.
Keywords
Alzheimer Disease/genetics, Alzheimer Disease/metabolism, Amino Acid Sequence, Amyloid beta-Protein Precursor/genetics, Brain/pathology, Glycine, Humans, Isoleucine, Point Mutation, Valine
Pubmed
Web of science
Create date
22/09/2011 17:24
Last modification date
20/08/2019 12:23
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