Key result
ACEI and statins alter human protein and gene expression and reduce tau pathology in mice.
Why the study?
Hypertension and hyperlipidemia are risk factors for Alzheimer's disease, and medications managing them may reduce dementia risk and serve as repurposed therapeutics.
Does treatment with ACE inhibitors and statins alter omics profiles and reduce tau pathology in human patients and transgenic mouse models of Alzheimer's disease?
Does treatment with ACE inhibitors and statins alter omics profiles and reduce tau pathology in human patients and transgenic mouse models of Alzheimer's disease?
ACE inhibitors and statins alter specific omics profiles and reduce tau pathology in preclinical models, suggesting potential as repurposed therapeutics for Alzheimer's disease.
May support ACEI/statins repurposing for tau pathology; hypothesis-generating and requires randomized human trials before clinical consideration.
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.
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Collu et al. (2023) studied Alzheimer's disease and tauopathies. Angiotensin-converting enzyme inhibitors (ACEI) and statins (STAT) was evaluated on Transcriptomic, proteomic and tau pathology profiles. Treatment with ACEI, statins, or their combination significantly altered specific protein and gene expressions in humans and reduced tau pathology in transgenic mice.
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