A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline

  title={A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline},
  author={Thorl{\'a}kur J{\'o}nsson and Jasvinder K. Atwal and Stacy Steinberg and J{\'o}n Snaedal and Palmi V. Jonsson and Sigurbjorn Bjornsson and Hreinn Stef{\'a}nsson and Patrick Sulem and Daniel Fannar Gudbjartsson and Janice A. Maloney and Kwame Hoyte and Amy Gustafson and Yichin Liu and Yanmei Lu and Tushar R. Bhangale and Robert R. Graham and Johanna Huttenlocher and Gyda Bjornsdottir and Ole Andreas Andreassen and Erik G. J{\"o}nsson and Aarno Palotie and Timothy W. Behrens and Olafur T Magnusson and Augustine Kong and Unnur Thorsteinsd{\'o}ttir and Ryan J. Watts and K{\'a}ri Stef{\'a}nsson},
The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer’s disease. [] Key Method Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer’s disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against…
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A rare gene variant has been found that decreases the peptide deposition seen in the brains of people with Alzheimer's disease, providing support for the hypothesis that reducing the beta-cleavage of APP may protect against Alzheimer's.
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Alzheimer's disease.
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C cultured cells which express a β-APP complementary DNA bearing a double mutation found in a Swedish FAD family produce ∼6–8-fold more Aβ than cells expressing normalβ-APP, and this increase is confirmed for elucidating the fundamental mechanism of Alzheimer's disease.
Epidemiology of Alzheimer disease.
  • R. MayeuxY. Stern
  • Biology, Psychology
    Cold Spring Harbor perspectives in medicine
  • 2012
The prevalence and incidence rates, the established environmental risk factors, and the protective factors are discussed, and genetic variants predisposing to disease are reviewed.
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Molecular genetics of Alzheimer’s disease
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Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study
Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as the population ages.
Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
The amyloid of Alzheimer's disease is similar in subunit size, composition but not sequence to the scrapie‐associated fibril and its constituent polypeptides, and the sequence and composition of NFT are not homologous to those of any of the known components of normal neurofilaments.
Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity
Asp2 is a new protein target for drugs that are designed to block the production of amyloid β-peptide peptide and the consequent formation ofAmyloid plaque in Alzheimer's disease.
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It is shown that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS.
Purification and cloning of amyloid precursor protein β-secretase from human brain
A membrane-bound enzyme activity that cleaves full-length APP at the β-secretase cleavage site is described and found to be the predominant β-cleavage activity in human brain, and it is found that human brain β- secretase is a new membrane- bound aspartic proteinase.