Molecular Analysis of the Presenilin 1 (S182) Gene in “Sporadic” Cases of Alzheimer's Disease: Identification and Characterisation of Unusual Splice Variants
Abstract
Mutations of the presenilin 1 (PS-1) gene at the Alzheimer's disease (AD) FAD3 locus on chromosome 14q24.3 are responsible for the majority of familial early-onset AD. As genes responsible for familial forms of AD are obvious candidates for further investigation in "sporadic" disease, we performed a molecular analysis of PS-1 transcripts extracted from brain tissues of a series of histologically confirmed cases of "sporadic" AD (n=10) and also from histologically "normal" (non-Alzheimer) age-matched brain controls (n=5). No sequence changes in the PS-1 coding sequence were detected after analysis by reverse transcription-PCR. This suggests that the frequency of mutations in the PS-1 (S182) coding region in "sporadic" Alzheimer's disease in very low. However, we demonstrated that the PS-1 gene is highly variably spliced. One splice variant involves the 5' untranslated region of the PS-1 gene only and hence encodes for normal PS-1. Six further splice variants involve coding regions of the PS-1 gene and result in truncated proteins lacking specific transmembrane domains. Most of these variants do not coincide with recognized sites of introns in the PS-1 gene. One of these variants, resulting in the loss of transmembrane domain TM-VII, was found only in an AD patient.
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The various PS1 polypeptides do not arise by alternative splicing.
“Because both the 49 and 32 kDa species seen in our expression systems derive from a full-length human PS1 cDNA, we can exclude the possibility that the various polypeptides arise by alternative splicing”
From Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain (1997) · cites this paper as Anwar et al., 1996
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Review Article: Genetics of Alzheimer Disease
Bekris, L. M., Yu, C.-E., Bird, T. D., & Tsuang, D. W. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710383571 · Cited by 1,029 · see citing works
Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain
Lah, J. J., Heilman, C. J., Nash, N. R., Rees, H. D., Yi, H., Counts, S. E., & Levey, A. I. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-06-01971.1997 · Cited by 168 · see citing works
“Because both the 49 and 32 kDa species seen in our expression systems derive from a full-length human PS1 cDNA, we can exclude the possibility that the various polypeptides arise by alternative splicing (Clark et al., 1995; Rogaev et al., 1995; Anwar et al., 1996; Sahara et al., 1996).”
BackgroundThe genes associated with early-onset Alzheimer’s disease
Dai, M.-H., Zheng, H., Zeng, L.-D., & Zhang, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.23738 · Cited by 171 · see citing works
The presenilin genes: a new gene family involved in Alzheimer disease pathology
Cruts, M., Hendriks, L., & Van Broeckhoven, C. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.supplement_1.1449 · Cited by 163 · see citing works
Hébert, S. S., Serneels, L., Dejaegere, T., Horré, K., Dąbrowski, M., Baert, V., Annaert, W. G., Hartmann, D., & Strooper, B. D. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.002 · Cited by 152 · see citing works
A Novel Presenilin‐2 Splice Variant in Human Alzheimer's Disease Brain Tissue
Sato, N., Hori, O., Yamaguchi, A., Lambert, J., Chartier‐Harlin, M., Robinson, P. A., Delacourte, A., Schmidt, A. M., Furuyama, T., Imaizumi, K., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722498.x · Cited by 121 · see citing works
“Human brain cDNA and mRNA Human brain cDNA from sporadic AD patients (30 samples) and age-matched controls (17 samples) was prepared as described before (Anwar et al., 1996).”
MethodSelf-citationHe, R., Lü, J., & Jun-Ye, M. I. A. O. (2010) · Science China Life Sciences · doi:10.1007/s11427-010-4112-3 · Cited by 105 · see citing works
Regulation of Apoptosis by Presenilin 1
Wolozin, B. L., Alexander, P., & Palacino, J. J. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00041-4 · Cited by 60 · see citing works
Expression of presenilin-1 and -2 mRNAs in rat and Alzheimer's disease brains
Takami, K., Terai, K., Matsuo, A., Walker, D. G., & McGeer, P. L. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01274-7 · Cited by 59 · see citing works
Tandon, A., & Fraser, P. E. (2002) · Genome biology · doi:10.1186/gb-2002-3-11-reviews3014 · Cited by 59 · see citing works
Kozak, M. (2000) · Genomics · doi:10.1006/geno.2000.6412 · Cited by 59 · see citing works
Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's disease.
Giannakopoulos, P., Bouras, C., Kövari, E., Shioi, J., Tezapsidis, N., Hof, P. R., & Robakis, N. K. (1997) · Europe PMC (PubMed Central) · Cited by 53 · see citing works
Identification of a human 5-HT6 receptor variant produced by alternative splicing
Olsen, M. A., Nawoschik, S. P., Schurman, B. R., et al. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00338-6 · Cited by 44 · see citing works
Quantification of presenilin‐1 mRNA in Alzheimer's disease brains
Johnston, J. A., Froelich, S., Lannfelt, L., & Cowburn, R. F. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00969-6 · Cited by 20 · see citing works
The structure and functions of the presenilins
Dewji, N. N. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-4566-9 · Cited by 18 · see citing works
Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes
Vidal, R., Ghiso, J. A., Wısnıewskı, T., & Frangione, B. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00845-9 · Cited by 18 · see citing works
Deng, G., Su, J. H., & Cotman, C. W. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00922-2 · Cited by 16 · see citing works
The Genetics of Alzheimer’s Disease and Parkinson’s Disease
Bekris, L., Yu, C.-E., Bird, T., & Tsuang, D. (2011) · Advances in neurobiology · doi:10.1007/978-1-4419-7104-3_21 · Cited by 14 · see citing works
“PSEN2 also displays tissue-specific alternative splicing (ADCG, 1995; Anwar et al., 1996; Hutton et al., 1996; Levy-Lahad et al., 1995; Prihar et al., 1996; Rogaev et al., 1995).”
BackgroundTanahashi, H., & Tabira, T. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.09.033 · Cited by 11 · see citing works
Proteins Implicated In Alzheimer Disease
Ermekova, K. S., Chang, A., Zambrano, N., de Candia, P., Russo, T., & Sudol, M. (1998) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-4869-0_10 · Cited by 11 · see citing works
Dauch, P., Champigny, G., Ricci, J., & Checler, F. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(96)13296-1 · Cited by 7 · see citing works
Etiological Clues from Gene Defects Causing Early Onset Familial Alzheimer’s Disease
Wasco, W., & Tanzi, R. E. (1997) · Humana Press eBooks · doi:10.1007/978-1-59259-471-9_1 · Cited by 7 · see citing works
Developmental Regulation and Possible Alternative Cleavage of Presenilin 1 in the Rat Retina
Bresciani, L. G., WALSH, D., Gentleman, S., & Jen, L. S. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2002.1169 · Cited by 6 · see citing works
Correct Heteroduplex Formation for Mutation Detection Analysis
Smith, M. J., Humphrey, K. E., Cappai, R., et al. (2000) · Molecular Diagnosis · doi:10.1007/bf03262025 · Cited by 5 · see citing works
Genetics of Alzheimer's Disease
Bekris, L. M., Yu, C., Bird, T. D., & Tsuang, D. W. (2010) · Wiley eBooks · doi:10.1002/9780470669600.ch43 · Cited by 5 · see citing works
Karaduman, T. (2020) · Türk doğa ve fen dergisi :/Türk doğa ve fen dergisi · doi:10.46810/tdfd.713624 · Cited by 2 · see citing works
“As well as some results showed that variations of PSEN1 have no effect on LOAD pathogenesis [17], there is also an evidence that PSEN1 rare variants have a contribution to this pathogenesis [13,15,16].”
BackgroundResultPresenilin-1 Immunoreactivity in Human Neurodegenerative Diseases
Giannakopoulos, P., K�vari, E., Canuto, A., Hof, P. R., & Bouras, C. (1999) · KARGER eBooks · doi:10.1159/000061433
Recombinant AAV Gene Therapy and Delivery
Carty, N. (2009) · Digital Commons - University of South Florida (University of South Florida)
Mann, D. M. A. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6001-2_4
- Authors
- Anwar, R., Moynihan, T. P., Ardley, H., Brindle, N., Coletta, P. L., Cairns, N., Markham, A. F., & Robinson, P. A.
- Affiliations
- St James's University Hospital (GB)
- Corresponding author
- Anwar, Rashida
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1996-04
- Volume
- 66
- Issue
- 4
- Pages
- 1774-1777
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2067108157
- Cited by
- 30
- References
- 0
- Citations by year
- 2020: 1 · 2017: 1
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- 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, Alzheimer's disease, sporadic Alzheimer's disease, alternative splicing, splice variants, truncated protein, 5' untranslated region
- MeSH terms
- Alzheimer Disease, Base Sequence, Humans, Membrane Proteins, Molecular Sequence Data, RNA, Polymerase Chain Reaction, Alternative Splicing, Presenilin-1
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