ArticleSleep2018
Melatonin receptor type 1A gene linked to Alzheimer's disease in old age.
Article in Sleep, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Dietary Melatonin Therapy Alleviates the Lamina Cribrosa Damages in Patients with Mild Cognitive Impairments: A Double-Blinded, Randomized Controlled Study.Medical science monitor : international medical journal of experimental and clinical research · 2020Trial
- Melatonin receptor signaling in human pathologies: from molecular mechanisms to therapeutic targets.Function (Oxford, England) · 2026Review
- Sleep Disorders in Neurodegenerative Diseases with Dementia: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review.Molecules (Basel, Switzerland) · 2025Review
- Pharmacological modulation of MRAP2 protein on murine melatonin receptor signaling.Frontiers in endocrinology · 2025Article
- Melatonin: A potential nighttime guardian against Alzheimer's.Molecular psychiatry · 2025Review
- Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.Neuroscience bulletin · 2024Article
- Microglial Melatonin Receptor 1 Degrades Pathological Alpha-Synuclein Through Activating LC3-Associated Phagocytosis In Vitro.CNS neuroscience & therapeutics · 2024Article
- Tryptophan Metabolism in Alzheimer's Disease with the Involvement of Microglia and Astrocyte Crosstalk and Gut-Brain Axis.Aging and disease · 2024Review
- Job-related exhaustion risk variant in UST is associated with dementia and DNA methylation.Scientific reports · 2024Article
- Melatonin alleviates oxidative stress damage in mouse testes induced by bisphenol A.Frontiers in cell and developmental biology · 2024Article
- Melatonin in Alzheimer's Disease: Literature Review and Therapeutic Trials.Journal of Alzheimer's disease : JAD · 2024Review
- Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.Coordination chemistry reviews · 2023Article
- Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling.CNS neuroscience & therapeutics · 2023Article
- Circadian rhythms in neurodegenerative disorders.Nature reviews. Neurology · 2022Review
- Amyloid Burden in Alzheimer's Disease Patients Is Associated with Alterations in Circadian Rhythm.Dementia and neurocognitive disorders · 2021Article
- Microglial MT1 activation inhibits LPS-induced neuroinflammation via regulation of metabolic reprogramming.Aging cell · 2021Article
- Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease.Progress in neurobiology · 2021Review
- Pharmacological Actions of Carbamate Insecticides at Mammalian Melatonin Receptors.The Journal of pharmacology and experimental therapeutics · 2021Article
- Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson's Disease.Frontiers in aging neuroscience · 2021Review
Corrections and comments
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Authors and funding
18 authors at 11 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disruption of the circadian rhythms is a frequent preclinical and clinical manifestation of Alzheimer's disease. Furthermore, it has been suggested that shift work is a risk factor for Alzheimer's disease. Previously, we have reported association of intolerance to shift work (job-related exhaustion in shift workers) with a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A) and linked to MTNR1A brain expression levels. Here, we studied association of that variant with clinical and neuropathological Alzheimer's disease in a Finnish whole-population cohort Vantaa 85+ (n = 512, participants over 85 years) and two follow-up cohorts. Rs12506228A was associated with clinical Alzheimer's disease (p = 0.000073). Analysis of post-mortem brain tissues showed association with higher amount of neurofibrillary tangles (p = 0.0039) and amyloid beta plaques (p = 0.0041). We then followed up the associations in two independent replication samples. Replication for the association with clinical Alzheimer's disease was detected in Kuopio 75+ (p = 0.012, n = 574), but not in the younger case-control sample (n = 651 + 669). While melatonin has been established in regulation of circadian rhythms, an independent role has been also shown for neuroprotection and specifically for anti-amyloidogenic effects. Indeed, in vitro, RNAi mediated silencing of MTNR1A increased the amyloidogenic processing of amyloid precursor protein (APP) in neurons, whereas overexpression decreased it. Our findings suggest variation close to MTNR1A as a shared genetic risk factor for intolerance to shift work and Alzheimer's disease in old age. The genetic associations are likely to be mediated by differences in MTNR1A expression, which, in turn, modulate APP metabolism.
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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.