A mutation in Alzheimerʼs disease destroying a splice acceptor site in the presenilin-1 gene

Pérez‐Tur, Jordi; Froelich, Susanne; Prihar, Guy; Crook, Richard; Baker, Matt; Duff, Karen; Wragg, Michelle; Busfield, Frances; Lendon, Corinne; Clark, Robert F.

doi:10.1097/00001756-199512000-00071

Cited by 241 publications

(83 citation statements)

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“…Woodruff et al knocked in the PSEN1ΔE9 mutation into a control background using TALEN-mediated genome editing (Woodruff et al, 2013). The PSEN1ΔE9 mutation causes a loss of exon 9 and the ability of PSEN1 protein to undergo endoproteolysis to its mature form (Perez-Tur et al, 1995). The control line in particular was generated by Venter, whose genome is publically available.…”

Section: Published Ipsc Modelsmentioning

confidence: 99%

Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models

Sproul

2015

Molecular Aspects of Medicine

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Section: Published Ipsc Modelsmentioning

confidence: 99%

Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models

Sproul

2015

Molecular Aspects of Medicine

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“…All except one of the PS1 mutations are missense mutations causing single amino acid changes. The exception is a mutation which destroys the splice acceptor site for exon 10 of PS1, resulting in an in-frame deletion of this exon and an amino acid substitution [21]. All FAD missense mutations identified to date occur in amino acids that are conserved between PS1p and PS2p.…”

Section: The Ps1 Gene and Its Expressionmentioning

confidence: 99%

Monogenic determinants of familial Alzheimer's disease: presenilin-1 mutations

Kovacs¹,

Tanzi²

1998

CMLS, Cell. Mol. Life Sci.

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Presenilin-1 (PS1) mutations account for the greatest portion of early onset familial Alzheimer's disease (FAD) cases. The exact cellular function of PS1 is not known. To date, PS1 mutations have been shown to alter two potential biological roles of the protein, either of which could make neurons more susceptible to neurodegeneration. First, PS1 mutations result in elevated A beta 42/A beta 40 ratios in plasma of FAD patients, in transgenic mice and in transfected cell lines. A beta 42 is the more hydrophobic and most neurotoxic form of the peptide. A common molecular event that has been associated with all of the known early onset FAD genes is the excessive production or accumulation of the A beta peptide in the brain. PS1 mutations have also been found to alter the Notch signalling pathway, but the mechanism by which this may affect neurodegeneration remains to be determined. Future studies will be needed to elucidate whether PS1 mutations lead directly to neuronal dysfunction and degeneration or cause cell death by increasing A beta 42 generation and deposition.

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“…Aβ42 has a greater tendency to aggregate than shorter Aβ species and is the first species to be deposited in the brains of transgenic animals carrying mutant human APP genes. Deletions of PSEN1 exon 9 may result either from either mutation at a splice acceptor site (ser290Cys or S290C) [17,74,90,126,146] or from deletions of several kilobases (4.6-5.9kb) of genomic DNA [31,68,69,130,152,175,176]. Biochemical studies suggest that it is the point mutation rather than the deletion per se which is critical for the pathological increase in Aβ42 production [157].…”

Section: Introductionmentioning

confidence: 99%

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

2005

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It is now 10 years since the first report of mutations in the presenilin genes that were deterministic for familial autosomal dominant Alzheimer's disease. The most common of these mutations occurs in the presenilin-1 gene (PSEN1) located on chromosome 14. In the ensuing decade, more than 100 PSEN1 mutations have been described. The emphasis of these reports has largely been on the novelty of the mutations and their potential pathogenic consequences rather than detailed clinical, neuropsychological, neuroimaging and neuropathological accounts of patients with the mutation. This article reviews the clinical phenotypes of reported PSEN1 mutations, emphasizing their heterogeneity, and suggesting that other factors, both genetic and epigenetic,must contribute to disease phenotype.

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A mutation in Alzheimerʼs disease destroying a splice acceptor site in the presenilin-1 gene

Cited by 241 publications

References 0 publications

Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models

Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models

Monogenic determinants of familial Alzheimer's disease: presenilin-1 mutations

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

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