ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Transgenic mice overexpressing amyloid precursor protein exhibit early metabolic deficits and a pathologically low leptin state associated with hypothalamic dysfunction in arcuate neuropeptide Y neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 104 citations in OpenAlex.
- Late-life body mass index and amyloid interaction on cognitive decline in unimpaired older adults.The journal of prevention of Alzheimer's disease · 2026Trial
- Zinc-mediated lysosomal activation by 1H10 enhances autophagy and attenuates tau pathology in Alzheimer's disease models.Molecular brain · 2026Article
- The cholinergic system exerts opposing effects on memory at different stages of disease progression in Alzheimer's and Down syndrome model systems.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Association of Alzheimer's disease biomarkers with malnutrition and altered body composition in cognitively impaired patients: a cross-sectional memory clinic study.Alzheimer's research & therapy · 2026Article
- Leptin as a Potential Modifier of Neuroinflammation: Contrasting Roles in Alzheimer's Disease and Multiple Sclerosis.International journal of molecular sciences · 2025Review
- Vulnerability of mitochondrial OXPHOS complexes in the arcuate nucleus of the hypothalamus of Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- Sex-specific changes in energy demand during the preplaque stage in a transgenic Alzheimer's mouse model.Biology of sex differences · 2025Article
- Hydrate to keep the amyloid away.Journal of Alzheimer's disease : JAD · 2025Article
- Early detection of Alzheimer's disease using the MEMORIES mnemonic.Chronic diseases and translational medicine · 2025Review
- Extracellular vesicles contribute to the beneficial effects of exercise training in APP/PS1 mice.iScience · 2025Article
- Evaluating the Efficacy of Levetiracetam on Non-Cognitive Symptoms and Pathology in a Tau Mouse Model.Biomedicines · 2024Article
- The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions.Neurology international · 2024Review
- Pharmacological enhancement of slow-wave activity at an early disease stage improves cognition and reduces amyloid pathology in a mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Effects of Menopause and High Fat Diet on Metabolic Outcomes in a Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Interictal spikes in Alzheimer's disease: Preclinical evidence for dominance of the dentate gyrus and cholinergic control by the medial septum.Neurobiology of disease · 2023Article
- Sex differences in metabolic phenotype and hypothalamic inflammation in the 3xTg-AD mouse model of Alzheimer's disease.Biology of sex differences · 2023Article
- Longitudinal Studies on Alzheimer Disease Mouse Models with Multiple Tracer PET/CT: Application of Reduction and Refinement Principles in Daily Practice to Safeguard Animal Welfare during Progressive Aging.Animals : an open access journal from MDPI · 2023Article
- Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia.International journal of molecular sciences · 2023Review
- Altered cortical and subcortical morphometric features and asymmetries in the subjective cognitive decline and mild cognitive impairment.Frontiers in neurology · 2023Article
- Towards an understanding of the pathological basis of senile depression and incident dementia: Implications for treatment.Psychiatry and clinical neurosciences · 2022Review
1 more citing papers are in PubMed but not listed here.
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Abstract
Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ.
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