ArticleAlzheimer's research & therapy2016
Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association with increasing amyloid-β and tau pathology.
Article in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 5 of them syntheses that pooled it.
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Who cites it
118 citing papers in PubMed, 5 syntheses or guidelines pooled it, 204 citations in OpenAlex.
- ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.Journal of translational medicine · 2023Pooled it
- Alzheimer's early detection in post-acute COVID-19 syndrome: a systematic review and expert consensus on preclinical assessments.Frontiers in aging neuroscience · 2023Pooled it
- Meta-Analysis of APP Expression Modulated by SARS-CoV-2 Infection via the ACE2 Receptor.International journal of molecular sciences · 2022Pooled it
- Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly: A Meta-Analysis.Hypertension (Dallas, Tex. : 1979) · 2021Pooled it
- Cognitive benefits of angiotensin IV and angiotensin-(1-7): A systematic review of experimental studies.Neuroscience and biobehavioral reviews · 2018Pooled it
- Association between renin angiotensin system and cognitive outcomes over 15 years: The Look AHEAD study.Journal of Alzheimer's disease : JAD · 2026Trial
- Associations of Angiotensin Converting Enzyme-1 and Angiotensin II Blood Levels and Cognitive Function.Journal of Alzheimer's disease : JAD · 2018Trial
- Protein Modifications and Quality Control System: Target for Alzheimer's Disease Therapy.International journal of molecular sciences · 2026Review
- Cerebrospinal fluid and frontal cortex TMPRSS2 and ACE2 protein levels differ in Down syndrome and Alzheimer's disease.Acta neuropathologica communications · 2026Article
- Microglial activation and RAS signaling: a dual-edged sword in neuroinflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Review
- Biophysical analysis of angiotensin II and amyloid-β cross-interaction in aggregation and membrane disruption.FEBS letters · 2026Article
- Neuroprotective effects of telmisartan in a harmaline-induced model of essential tremor: modulation of the renin-angiotensin system and inflammatory pathways.Frontiers in pharmacology · 2026Article
- Nitric Oxide at the Nexus of ACE2 Biology and COVID-19: Implications for Cardiovascular and Neurodegenerative Comorbidities.Physiological research · 2025Review
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
- Salt-sensitive hypertension promotes neuronal mitochondrial stress and neurodegenerative alterations via neuro-vascular metabolic reprogramming and local RAS signaling.Journal of neuroinflammation · 2025Article
- The dual role of ACE2 in viral infections and neurodegeneration: mechanisms and therapeutic opportunities.Journal of neurovirology · 2025Review
- Expression of SARS-CoV-2 entry receptor ACE2 in human brain and its association with Alzheimer's disease and COVID-19.Molecular psychiatry · 2025Review
- Angiotensin-(1-7) protective effects in neurocognitive disorders: molecular mechanisms to therapeutic implications.Frontiers in physiology · 2025Review
- Neurological, psychological, psychosocial complications of long-COVID and their management.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
58 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity.
methodsWe measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores.
resultsACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = -0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = -0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = -0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1-7) (a proxy measure of ACE-2 activity indicating conversion of Ang II to Ang (1-7)) is reduced in AD.
conclusionsTogether, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD.
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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.