Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change.
| Title: | Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change. |
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| Authors: | Rasmussen LT; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil.; Department of Biomedicine, University Center of the Integrated Faculties of Ourinhos (Unifio), Ourinhos, São Paulo, Brazil.; de Labio RW; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil.; Dos Santos MP; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil.; Fredi BM; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil.; Baisi Chagas EF; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil.; Department of Physical Education, University of Marilia (Unimar), Marilia, São Paulo, Brazil.; Chen ES; Department of Morphology and Genetics, Federal University of São Paulo (Unifesp), São Paulo, Brazil.; Turecki G; Departments of Psychiatry, Human Genetics, and Neurology & Neurosurgery, Bell Canada Brain Bank (Douglas Mental Health University Institute), Montreal, Quebec, Canada.; Smith MAC; Department of Morphology and Genetics, Federal University of São Paulo (Unifesp), São Paulo, Brazil.; Payão SLM; Department of Genetics, Marilia Medical School (Famema), Marilia, São Paulo, Brazil. |
| Source: | The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2024 May 01; Vol. 79 (5). |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: published on behalf of the Gerontological Society of America by Oxford University Press Country of Publication: United States NLM ID: 9502837 Publication Model: Print Cited Medium: Internet ISSN: 1758-535X (Electronic) Linking ISSN: 10795006 NLM ISO Abbreviation: J Gerontol A Biol Sci Med Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : published on behalf of the Gerontological Society of America by Oxford University Press; Original Publication: Washington, DC : Gerontological Society of America, c1995- |
| MeSH Terms: | Alzheimer Disease*/genetics ; Alzheimer Disease*/metabolism ; Low Density Lipoprotein Receptor-Related Protein-1*/genetics ; Antigens, CD*; Cerebellum/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptor, Insulin/genetics ; Receptor, Insulin/metabolism ; Auditory Cortex/metabolism ; Amyloid beta-Protein Precursor/genetics ; Apolipoproteins E/genetics ; Gene Expression/genetics ; Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Case-Control Studies |
| Abstract: | Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.; (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Grant Information: | 2015/24699-9 São Paulo Research Foundation |
| Contributed Indexing: | Keywords: APOE; APP; GRIN2B; INSR; LRP1; Gene expression |
| Substance Nomenclature: | 0 (Low Density Lipoprotein Receptor-Related Protein-1); 0 (LRP1 protein, human); 0 (Receptors, N-Methyl-D-Aspartate); EC 2.7.10.1 (Receptor, Insulin); EC 2.7.10.1 (INSR protein, human); 0 (NR2B NMDA receptor); 0 (Amyloid beta-Protein Precursor); 0 (Apolipoproteins E); 0 (Antigens, CD) |
| Entry Date(s): | Date Created: 20240124 Date Completed: 20240425 Latest Revision: 20250623 |
| Update Code: | 20260130 |
| DOI: | 10.1093/gerona/glae023 |
| PMID: | 38267766 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't