Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice
Background: Hypertension and hyperlipidemia are considered risk factors for Alzheimer’s disease (AD) and other related dementias. Clinically approved medications typically prescribed to manage these conditions have shown an association with reduced risk of developing AD and could be explored as pote...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223015548 |
| _version_ | 1797630598528892928 |
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| author | Roberto Collu Elisa Giunti Sarah Daley Mei Chen Weiming Xia |
| author_facet | Roberto Collu Elisa Giunti Sarah Daley Mei Chen Weiming Xia |
| author_sort | Roberto Collu |
| collection | DOAJ |
| description | Background: Hypertension and hyperlipidemia are considered risk factors for Alzheimer’s disease (AD) and other related dementias. Clinically approved medications typically prescribed to manage these conditions have shown an association with reduced risk of developing AD and could be explored as potential repurposed therapeutics. Objective: We aimed to explore the effects of the pharmacological treatment with angiotensin-converting enzyme inhibitors (ACEI) and statins (STAT) on AD-related neuropathology and the potential benefits of their concurrent use. Methods: We investigated the effect of ACEI, STAT or combination of both by exploring the transcriptomic, proteomic and tau pathology profiles after treatment in both human patients and in P301S transgenic mice (PS19) modeling tauopathies and AD. We performed bioinformatic analysis of enriched pathways after treatment. Results: Proteomics and transcriptomics analysis revealed proteins and genes whose expression is significantly changed in subjects receiving treatment with ACEI, STAT or combined drugs. In mice, treatment with the ACEI lisinopril significantly decreased brain levels of total tau (Tau) and phosphorylated tau (pTau)-181, while the STAT atorvastatin significantly reduced the levels of pTau-396. The combined therapy with lisinopril and atorvastatin significantly decreased Tau. Moreover, brain levels of lisinopril were negatively correlated with Tau. Among the others, CD200, ADAM22, BCAN and NCAM1 were significantly affected by treatments in both human subjects and transgenic mice. Conclusions: Our findings provide significant information that may guide future investigation of the potential use of ACEI, STAT, or the combination of the two drug classes as repurposed therapies or preventive strategies for AD and other neurodegenerative diseases. |
| first_indexed | 2024-03-11T11:10:30Z |
| format | Article |
| id | doaj.art-582605138ccc4bbb99239219f48bcd68 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T11:10:30Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-582605138ccc4bbb99239219f48bcd682023-11-12T04:39:12ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01168115756Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau miceRoberto Collu0Elisa Giunti1Sarah Daley2Mei Chen3Weiming Xia4Geriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United States; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United StatesGeriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United States; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United StatesGeriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United States; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United StatesGeriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United StatesGeriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United States; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States; Department of Biological Sciences, University of Massachusetts Kennedy College of Science, Lowell, MA, United States; Correspondence to: 200 Springs Road, Building 70–202, Bedford VA Healthcare System, Bedford, MA 01730, United States.Background: Hypertension and hyperlipidemia are considered risk factors for Alzheimer’s disease (AD) and other related dementias. Clinically approved medications typically prescribed to manage these conditions have shown an association with reduced risk of developing AD and could be explored as potential repurposed therapeutics. Objective: We aimed to explore the effects of the pharmacological treatment with angiotensin-converting enzyme inhibitors (ACEI) and statins (STAT) on AD-related neuropathology and the potential benefits of their concurrent use. Methods: We investigated the effect of ACEI, STAT or combination of both by exploring the transcriptomic, proteomic and tau pathology profiles after treatment in both human patients and in P301S transgenic mice (PS19) modeling tauopathies and AD. We performed bioinformatic analysis of enriched pathways after treatment. Results: Proteomics and transcriptomics analysis revealed proteins and genes whose expression is significantly changed in subjects receiving treatment with ACEI, STAT or combined drugs. In mice, treatment with the ACEI lisinopril significantly decreased brain levels of total tau (Tau) and phosphorylated tau (pTau)-181, while the STAT atorvastatin significantly reduced the levels of pTau-396. The combined therapy with lisinopril and atorvastatin significantly decreased Tau. Moreover, brain levels of lisinopril were negatively correlated with Tau. Among the others, CD200, ADAM22, BCAN and NCAM1 were significantly affected by treatments in both human subjects and transgenic mice. Conclusions: Our findings provide significant information that may guide future investigation of the potential use of ACEI, STAT, or the combination of the two drug classes as repurposed therapies or preventive strategies for AD and other neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S0753332223015548Alzheimer’s diseaseACEIStatinsPS19TauProteomic |
| spellingShingle | Roberto Collu Elisa Giunti Sarah Daley Mei Chen Weiming Xia Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice Biomedicine & Pharmacotherapy Alzheimer’s disease ACEI Statins PS19 Tau Proteomic |
| title | Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice |
| title_full | Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice |
| title_fullStr | Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice |
| title_full_unstemmed | Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice |
| title_short | Angiotensin-converting enzyme inhibitors and statins therapies-induced changes in omics profiles in humans and transgenic tau mice |
| title_sort | angiotensin converting enzyme inhibitors and statins therapies induced changes in omics profiles in humans and transgenic tau mice |
| topic | Alzheimer’s disease ACEI Statins PS19 Tau Proteomic |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223015548 |
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