ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017
Angiotensin IV Receptors Mediate the Cognitive and Cerebrovascular Benefits of Losartan in a Mouse Model of Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- The relationship between renin-angiotensin system-modulating medication and depression: a systematic review.Translational psychiatry · 2026Pooled it
- Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease.Stem cell research & therapy · 2025Review
- Hemodynamic and neuronal contributions to low-frequency vascular oscillations in a preclinical model of Alzheimer's disease.Neurophotonics · 2025Article
- Anti-aging properties of the aminosterols of the dogfish shark.npj aging · 2024Review
- Neuronal ACE1 knockout disrupts the hippocampal renin angiotensin system leading to memory impairment and vascular loss in normal aging.Neurobiology of disease · 2024Article
- Genetic Appraisal of RAAS-Associated SNPs: REN (rs16853055), AGT (rs3789678) and ACE (rs4305) in Preeclamptic Women Living with HIV Infection.Current hypertension reports · 2024Review
- Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals.Biological psychiatry global open science · 2024Article
- Angiotensin Receptor Blockers and Cognition: a Scoping Review.Current hypertension reports · 2024Article
- Review
- Soluble and insoluble protein aggregates, endoplasmic reticulum stress, and vascular dysfunction in Alzheimer's disease and cardiovascular diseases.GeroScience · 2023Review
- Angiotensin receptor blocker use is associated with upregulation of the memory-protective angiotensin type 4 receptor (ATGeroScience · 2023Article
- Deciphering mechanisms of action of ACE inhibitors in neurodegeneration usingFrontiers in neuroscience · 2023Review
- Chronic Kidney Disease and Cognitive Impairment: The Kidney-Brain Axis.Kidney diseases (Basel, Switzerland) · 2022Review
- AT1 Receptors: Their Actions from Hypertension to Cognitive Impairment.Cardiovascular toxicology · 2022Review
- Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Angiotensin-(1-7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage.Frontiers in immunology · 2022Review
- A functional cerebral endothelium is necessary to protect against cognitive decline.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Brain Renin-Angiotensin System as Novel and Potential Therapeutic Target for Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Early manifestation of gait alterations in the Tg2576 mouse model of Alzheimer's disease.GeroScience · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The use of angiotensin receptor blockers (ARBs) correlates with reduced onset and progression of Alzheimer's disease (AD). The mechanism depicting how ARBs such as losartan restore cerebrovascular and cognitive deficits in AD is unknown. Here, we propose a mechanism underlying losartan's benefits by selectively blocking the effects of angiotensin IV (AngIV) at its receptor (AT4R) with divalinal in mice overexpressing the AD-related Swedish and Indiana mutations of the human amyloid precursor protein (APP mice) and WT mice. Young (3-month-old) mice were treated with losartan (∼10 mg/kg/d, 4 months), followed by intracerebroventricular administration of vehicle or divalinal in the final month of treatment. Spatial learning and memory were assessed using Morris water mazes at 3 and 4 months of losartan treatment. Cerebrovascular reactivity and whisker-evoked neurovascular coupling responses were measured at end point (∼7 months of age), together with biomarkers related to neuronal and vascular oxidative stress (superoxide dismutase-2), neuroinflammation (astroglial and microglial activation), neurogenesis (BrdU-labeled newborn cells), and amyloidosis [soluble amyloid-β (Aβ) species and Aβ plaque load]. Divalinal countered losartan's capacity to rescue spatial learning and memory and blocked losartan's benefits on dilatory function and baseline nitric oxide bioavailability. Divalinal reverted losartan's anti-inflammatory effects, but failed to modify losartan-mediated reductions in oxidative stress. Neither losartan nor divalinal affected arterial blood pressure or significantly altered the amyloid pathology in APP mice. Our findings identify activation of the AngIV/AT4R cascade as the underlying mechanism in losartan's benefits and a target that could restore Aβ-related cognitive and cerebrovascular deficits in AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.