ArticleMolecular psychiatry2022
Brain copper may protect from cognitive decline and Alzheimer's disease pathology: a community-based study.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Endocrine-Immune Crosstalk in Pediatric Autoimmune Diseases: A Systematic Review of the Role of Micronutrients, with Emphasis on Vitamin D.Nutrients · 2026Pooled it
- Targeting Copper in Cancer: Chelators to Counteract Cuproplasia and Ionophores to Promote Cuproptosis.Journal of medicinal chemistry · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Aging at the Crossroads of Cuproptosis and Ferroptosis: From Molecular Pathways to Age-Related Pathologies and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- From cooperation to collapse: the diet-microbiota-host gene triad in disease and aging.Frontiers in microbiomes · 2026Review
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- Neuroferroptosis in health and diseases.Nature reviews. Neuroscience · 2025Review
- Association between dietary copper intake and cognitive function in American older adults: NHANES 2011-2014.Scientific reports · 2025Observational
- Association between Copper Exposure and Cognitive Function: A Cross-Sectional Study in a County, Guangxi, China.Biological trace element research · 2025Article
- Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia.Metallomics : integrated biometal science · 2025Article
- Brain tissue metal concentrations and Alzheimer's disease neuropathology in total joint arthroplasty patients versus controls.Acta neuropathologica · 2025Article
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper.Metallomics : integrated biometal science · 2024Article
- Is Copper Still Safe for Us? What Do We Know and What Are the Latest Literature Statements?Current issues in molecular biology · 2024Review
- Myelin Pathology in Alzheimer's Disease: Potential Therapeutic Opportunities.Aging and disease · 2024Review
- MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.Frontiers in neuroscience · 2024Review
- Cuproptosis in stroke: focusing on pathogenesis and treatment.Frontiers in molecular neuroscience · 2024Review
- Cu(ATSM) Increases P-Glycoprotein Expression and Function at the Blood-Brain Barrier in C57BL6/J Mice.Pharmaceutics · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Copper is an essential micronutrient for brain health and dyshomeostasis of copper could have a pathophysiological role in Alzheimer's disease (AD), however, there are limited data from community-based samples. In this study, we investigate the association of brain copper (assessed using ICP-MS in four regions -inferior temporal, mid-frontal, anterior cingulate, and cerebellum) and dietary copper with cognitive decline and AD pathology burden (a quantitative summary of neurofibrillary tangles, diffuse and neuritic plaques in multiple brain regions) at autopsy examination among deceased participants (N = 657; age of death: 90.2(±6.2)years, 70% women, 25% APOE-ɛ4 carriers) in the Rush Memory and Aging Project. During annual visits, these participants completed cognitive assessments using a 19-test battery and dietary assessments (using a food frequency questionnaire). Regression, linear mixed-effects, and logistic models adjusted for age at death, sex, education, and APOE-ε4 status were used. Higher composite brain copper levels were associated with slower cognitive decline (β(SE) = 0.028(0.01), p = 0.001) and less global AD pathology (β(SE) = -0.069(0.02), p = 0.0004). Participants in the middle and highest tertile of dietary copper had slower cognitive decline (T2vs.T1: β = 0.038, p = 0.0008; T3vs.T1: β = 0.028, p = 0.01) than those in the lowest tertile. Dietary copper intake was not associated with brain copper levels or AD pathology. Associations of higher brain copper levels with slower cognitive decline and with less AD pathology support a role for copper dyshomeostasis in AD pathogenesis and suggest that lower brain copper may exacerbate or indicate disease severity. Dietary and brain copper are unrelated but dietary copper is associated with slower cognitive decline via an unknown mechanism.
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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.