Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

@article{Goate1991SegregationOA,
  title={Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease},
  author={Alison M. Goate and Marie Christine Chartier-Harlin and Mike Mullan and Jeremy S. Brown and Fiona Crawford and Liana Fidani and LuisA. Giuffra and Andrew R. Haynes and Nicholas G. Irving and Louise James and Rebecca Mant and P. J. Newton and Karen Rooke and Penelope Roques and Chris J. Talbot and Margaret A. Pericak-Vance and A. D. Roses and R. Williamson and Martin N. Rossor and Mike J. Owen and John Hardy},
  journal={Nature},
  year={1991},
  volume={349},
  pages={704-706}
}
A LOCUS segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21 (ref. 1), close to the amyloid precursor protein (APP) gene2–5. Recombinants between the APP gene and the AD locus have been reported6–8 which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous9. Families with late-onset AD do not show linkage to chromosome 21 markers9,10… 

Clinical features of early onset, familial Alzheimer's disease linked to chromosome 14.

TLDR
The clinical features and genetic analysis of a British pedigree with early onset AD in which neither the beta APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14.

Assessment of amyloid beta-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases.

TLDR
No APP gene mutations were found in any of the FAD families or sporadic-AD samples examined in this study, suggesting that the mutations in exons 16 and 17 are a rare cause of FAD.

Search for the Genes Responsible for Familial Alzheimer's Disease

TLDR
A common basis for the etiology of this devastating disorder can be discerned as different gene defects responsible for various forms of FAD are discovered.

Progress in Molecular Genetics of Alzheimer's Disease

TLDR
The emerging picture is that AD is a genetically complex, heterogeneous disorder and how these genetic factors interact with each other and with other yet-to-be-identified genetic and nongenetic factors to produce the clinical and pathologic findings in AD remains to be elucidated.

Genetic risk factors in familial Alzheimer's disease

Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease

TLDR
A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein.

Genetic dissection of Alzheimer disease, a heterogeneous disorder.

  • G. Schellenberg
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD and appears to act as a dose-dependent age-of-onsett modifier.

Genetic heterogeneity of gene defects responsible for familial Alzheimer disease

TLDR
This review provides a historical perspective of the search for FAD gene defects and summarizes the progress made in world-wide attempts to isolate and characterize the genes responsible for this disorder.

Molecular genetics of Alzheimer's disease

  • J. Hardy
  • Biology
    Biochemical Society transactions
  • 1989
TLDR
The occurrence and effects of the mutations in APP and the fact that the ε4 allele of ApoE are genetic risk factors point to the hypothesis that the extracellular deposition of β‐amyloid is the key initiating event in the pathogenesis of AD.

Genetic counseling in a Swedish Alzheimer family with amyloid precursor protein mutation.

TLDR
Genetic counseling in three family members is described, believed to be the first time presymptomatic genetic testing for AD has been reported, in members of the family who were at risk of inheriting the disease and who demanded the information.
...

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