ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 142 citations in OpenAlex.
- Unraveling the Role of LRP1 in Alzheimer's Disease: A Focus on Aβ Clearance and the Liver-Brain Axis.Journal of molecular neuroscience : MN · 2025Pooled it
- Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.Scientific reports · 2017Pooled it
- LRP1 Activation Promotes Metabolic Reprogramming and Mrc1 Expression to Attenuate LPS-Induced Cognitive Deficits: An Integrated Omics Analysis.CNS neuroscience & therapeutics · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- LRP1 facilitates Jamestown Canyon virus infection of neurons.Journal of virology · 2025Article
- Syringic Acid in Canarium odontophyllum for Diabetes and Obesity - A Review.Cell biochemistry and biophysics · 2025Review
- Review
- The Link Between Circadian Disruption and Alzheimer's Disease and Related Dementias: Insights from Peripheral Inflammation.Current opinion in physiology · 2025Article
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Disease-disease interactions: molecular links of neurodegenerative diseases with cancer, viral infections, and type 2 diabetes.Translational neurodegeneration · 2025Review
- Exploring LRP-1 in the liver-brain axis: implications for Alzheimer's disease.Molecular biology reports · 2025Review
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- The low-density lipoprotein receptor-related protein-1 (LRP1) in Schwann cells controls mitochondria homeostasis in peripheral nerves.Progress in neurobiology · 2025Article
- The role of protein lactylation in brain health and disease: current advances and future directions.Cell death discovery · 2025Review
- "Hyperglycemic Memory": Observational Evidence to Experimental Inference.Current diabetes reviews · 2025Review
- Article
- LRP1 at the crossroads of Aβ clearance and therapeutic targeting in Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat.CNS neuroscience & therapeutics · 2024Article
- Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.International journal of molecular sciences · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy.
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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.