ArticleJournal of neurochemistry2008
High cholesterol-induced neuroinflammation and amyloid precursor protein processing correlate with loss of working memory in mice.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 2 of them syntheses that pooled it.
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Who cites it
174 citing papers in PubMed, 2 syntheses or guidelines pooled it, 360 citations in OpenAlex.
- Lipid levels and the risk of dementia: A dose-response meta-analysis of prospective cohort studies.Annals of clinical and translational neurology · 2022Pooled it
- A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson's disease.Lipids in health and disease · 2020Pooled it
- Punica granatum L. peel extract mitigates hyperlipidemia-induced cognitive impairments in zebrafish larvae via modulating LXR signaling.Metabolic brain disease · 2026Article
- Unifying the hallmarks of major depression through neuroimmune-metabolic-oxidative (NIMETOX) dysregulation: a mechanistic systems framework.Cellular & molecular immunology · 2026Review
- Reproductive history differentially shapes the neural response of middle-aged hAPOEɛ4 female rats to estradiol therapy after a metabolic challenge.Biology of sex differences · 2026Article
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Minocycline Ameliorates Cognitive Impairments Without Modulating Microglial Reactivity in Sporadic Hypercholesterolemia: A Sex-Specific Analysis in Mice.Molecular neurobiology · 2025Article
- A simple nomogram to predict the onset of dementia in mild cognitive impairment: A retrospective study.Journal of Alzheimer's disease : JAD · 2025Article
- Retarded Learning in a Rabbit Model of Metabolic Syndrome Created by Long-Term Feeding of High-Fat Diet and High Sucrose.Nutrients · 2025Article
- Brain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.Acta neurologica Belgica · 2025Review
- Hypercholesterolemia drives microglial dysfunction and weakens response to amyloid plaques.Experimental neurology · 2025Article
- LDL Exposure Disrupts Mitochondrial Function and Dynamics in a Hippocampal Neuronal Cell Line.Molecular neurobiology · 2025Article
- Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo ECellular and molecular neurobiology · 2025Article
- Hypercholesterolemia, oxidative stress, and low-grade inflammation: a potentially dangerous scenario to blood-brain barrier.Metabolic brain disease · 2025Review
- ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.Scientific reports · 2025Article
- Lipids dysregulation in diseases: core concepts, targets and treatment strategies.Lipids in health and disease · 2025Review
- Metabolic disorders after traumatic brain injury: a narrative review of systemic consequences.Metabolic brain disease · 2025Review
- Gene expression patterns of the LDL receptor and its inhibitor Pcsk9 in the adult zebrafish brain suggest a possible role in neurogenesis.The European journal of neuroscience · 2025Article
- Traumatic Brain Injury in Mice Generates Early-Stage Alzheimer's Disease Related Protein Pathology that Correlates with Neurobehavioral Deficits.Molecular neurobiology · 2024Article
114 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Recent findings suggest that hypercholesterolemia may contribute to the onset of Alzheimer's disease-like dementia but the underlying mechanisms remain unknown. In this study, we evaluated the cognitive performance in rodent models of hypercholesterolemia in relation to neuroinflammatory changes and amyloid precursor protein (APP) processing, the two key parameters of Alzheimer's disease pathogenesis. Groups of normal C57BL/6 and low density lipoprotein receptor (LDLR)-deficient mice were fed a high fat/cholesterol diet for an 8-week period and tested for memory in a radial arm maze. It was found that the C57BL/6 mice receiving a high fat diet were deficient in handling an increasing working memory load compared with counterparts receiving a control diet while the hypercholesterolemic LDLR-/- mice showed impaired working memory regardless of diet. Immunohistochemical analysis revealed the presence of activated microglia and astrocytes in the hippocampi from high fat-fed C57BL/6 mice and LDLR-/- mice. Consistent with a neuroinflammatory response, the hyperlipidemic mice showed increased expression of cytokines/mediators including tumor necrosis factor-alpha, interleukin-1beta and -6, nitric oxide synthase 2, and cycloxygenase 2. There was also an induced expression of the key APP processing enzyme i.e. beta-site APP cleaving enzyme 1 in both high fat/cholesterol-fed C57BL/6 and LDLR-/- mice accompanied by an increased generation of C-terminal fragments of APP. Although ELISA for beta-amyloid failed to record significant changes in the non-transgenic mice, a threefold increase in beta-amyloid 40 accumulation was apparent in a strain of transgenic mice expressing wild-type human APP on high fat/cholesterol diet. The findings link hypercholesterolemia with cognitive dysfunction potentially mediated by increased neuroinflammation and APP processing in a non-transgenic mouse model.
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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 Socratic graph.