ArticleMolecular neurodegeneration2016
Chronic adiponectin deficiency leads to Alzheimer's disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 2 of them syntheses that pooled it.
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Who cites it
103 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- The Impact of Exercise Training on the Brain and Cognition in Type 2 Diabetes, and its Physiological Mediators: A Systematic Review.Sports medicine - open · 2025Pooled it
- The role of adiponectin in Alzheimer's disease: A translational review.The journal of nutrition, health & aging · 2024Pooled it
- Adipokines as Regulators of Nitric Oxide Synthase Isoforms Across Organs: Emerging Implications for Gastrointestinal Motility.International journal of molecular sciences · 2026Review
- Vitamin D and L-Cysteine as Potential Regulators of Adiponectin in Alzheimer's Disease: A Narrative Review.Nutrients · 2026Review
- Adiponectin Fortifies White Matter After Chronic Hypoperfusion-Induced Vascular Dementia.Stroke · 2026Article
- The role of adiponectin and cytokines in Amyotrophic lateral sclerosis: assessment of disease progression and survival status.Scientific reports · 2026Article
- Adiponectin and aging: Mechanistic insights, clinical paradox, and therapeutic horizons.Ageing research reviews · 2026Review
- Inhaled General Anesthetics in Alzheimer's Disease Progression: Divergent Effects, Underlying Mechanisms, and Future Perspectives.Molecular neurobiology · 2026Review
- The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus.Aging cell · 2026Article
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Adiponectin deficiency drives cerebrovascular dysfunction and synergizes with amyloid-β to exacerbate alzheimer's pathology.Alzheimer's research & therapy · 2026Article
- Circulating adipokines level and the risk of neurodegenerative diseases: a two‑sample mendelian randomization study and proteomic analysis.BMC neurology · 2026Article
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- Is Adipose Tissue Inflammation the Culprit of Obesity-Associated Comorbidities?Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Adipokines at the Metabolic-Brain Interface: Therapeutic Modulation by Antidiabetic Agents and Natural Compounds in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Fat talks first: how adipose tissue sets the pace of aging?Life medicine · 2025Review
- Epigenetic markers of disease risk and psychotherapy response in anxiety disorders - a longitudinal analysis of the DNA methylome.Molecular psychiatry · 2025Article
- Adiponectin Receptor Agonist Ameliorates Synaptic Dysfunction in 3xTg Alzheimer's Disease Mouse Model by Activation of AMPK.CNS neuroscience & therapeutics · 2025Article
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInsulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer's-like pathology in mice.
methodsTo study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment.
resultsAged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ
conclusionOur results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.
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