Cited by 102Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Increased Aβ42(43) from cell lines expressing presenilin 1 mutations

Mehta, Nitin D., Refolo, Lawrence M., Eckman, Chris, Sanders, Sunny, Yager, Debra, Perez‐Tur, Jordi, Younkin, Steve, Duff, Karen +2 more·1998·Annals of Neurology

Abstract

Mutations in the presenilin 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early‐onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild‐type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Aβ42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice‐out mutation (δ9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.

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  • Familial EOAD mutations in PSEN1 and PSEN2 typically result in an increased production of longer and more aggregation-prone derivatives of APP such as Aβ1-42.

    “familial EOAD mutations in PSEN1 and PSEN2 typically result in an increased production of longer and more aggregation-prone derivatives of APP such as Aβ1–42 [47–49].”

    From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [48]

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Authors
Mehta, N. D., Refolo, L. M., Eckman, C., Sanders, S., Yager, D., Perez‐Tur, J., Younkin, S., Duff, K., Hardy, J., & Hutton, M.
Affiliations
Mayo Clinic (US)
Corresponding author
Hardy, John
Venue
Annals of Neurology
Publisher
Wiley
Published
1998-02
Volume
43
Issue
2
Pages
256-258
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W1987287896
Cited by
101
References
21
Citations by year
2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 2
FWCI
7.78
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG 146133)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
presenilin 1, APP processing, amyloid-beta 42, Alzheimer's disease, presenilin 1 mutations, age of onset, autosomal dominant Alzheimer's disease, cell lines
MeSH terms
Alzheimer Disease, Analysis of Variance, Cell Line, Chromosomes, Human, Pair 14, Clone Cells, Gene Expression Regulation, Humans, Kidney, Membrane Proteins, Transfection, Blotting, Western, Point Mutation, Age of Onset, DNA, Complementary, Presenilin-1

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