The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Aβ 42/40 ratios
Abstract
Gene knockout studies in mice suggest that presenilin 1 (PS1) is the major γ‐secretase and that it contributes disproportionately to amyloid β (Aβ) peptide generation from β‐amyloid precursor protein (APP), whereas PS2 plays a more minor role. Based on this and other observations we hypothesized that familial Alzheimer's disease (FAD) mutations in PS2 would have a dramatic effect on function in order to have an observable effect on Aβ levels in the presence of normal PS1 alleles. Only four of the eight reported FAD mutations in PS2 have altered function in vitro suggesting that the other variants represent rare polymorphisms rather than disease‐causing mutations. In support of our hypothesis, the four verified PS2 FAD mutations cause substantial changes in the Aβ 42/40 ratio, comparable with PS1 mutations that cause very‐early‐onset FAD. Most of the PS2 mutations also cause a significant decrease in Aβ 40, APP C‐terminal fragment (CTF)γ and Notch intracellular domain (NICD) production suggesting that they are partial loss of function mutations. PS2 M239V, its PS1 homolog M233V, and other FAD mutations within transmembrane (TM) 5 of PS1 differentially affect CTFγ and NICD production suggesting that TM5 of PS are important for γ‐secretase cleavage of APP but not Notch.
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Self-citationCloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
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Candidate gene for the chromosome 1 familial Alzheimer’s disease locus
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., et al. (1995) · Science · doi:10.1126/science.7638622 · Cited by 2,577
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Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
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Mutations in APP have independent effects on Aβ and CTFγ generation
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Comprehensive Review on Alzheimer’s Disease: Causes and Treatment
Breijyeh, Z., & Karaman, R. (2020) · Molecules · doi:10.3390/molecules25245789 · Cited by 2,789
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836
The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal
Hardy, J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06181.x · Cited by 814
Alzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626
Babulal, G. M., Quiroz, Y. T., Albensi, B. C., Arenaza‐Urquijo, E., Astell, A. J., Babiloni, C., Bahar‐Fuchs, A., Bell, J., Bowman, G. L., Brickman, A. M., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.09.009 · Cited by 528
Metadata
- Authors
- Walker, E. S., Martinez, M., Brunkan, A. L., & Goate, A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2004-12-09
- Volume
- 92
- Issue
- 2
- Pages
- 294-301
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2088858515
- Cited by
- 177
- References
- 7
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
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- Walker, E. S., Martinez, M., Brunkan, A. L., & Goate, A. (2005). Presenilin 2 familial Alzheimer's disease mutations result in partial loss of function and dramatic changes in Aβ 42/40 ratios. Journal of Neurochemistry. https://doi.org/10.1111/j.1471-4159.2004.02858.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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