ArticleNeurobiology of aging2015
Acyl-coenzyme A:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer's disease mouse and reduces human P301L-tau content at the presymptomatic stage.
Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 93 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Article
- Implications of autolysosome- astrocyte-associated signature in the pathogenesis of Alzheimer's disease: evidence from artificial intelligence and multi-omics and clinical validation.Frontiers in neuroscience · 2026Article
- Inhibition of Acyl-CoenzymeA: Cholesterol Acyltransferase 1 promotes shedding of soluble triggering receptor on myeloid cells 2 (TREM2) and low-density lipoprotein receptor 1 (LRP1)-dependent phagocytosis of amyloid beta protein in microglia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases.Nature metabolism · 2025Article
- Macrophage polarization-related gene SOAT1 is involved in inflammatory response and functional recovery after spinal cord injury.Molecular and cellular biochemistry · 2025Article
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Connexin43 Contributes to Alzheimer's Disease by Promoting the Mitochondria-Associated Membrane-Related Autophagy Inhibition.Molecular neurobiology · 2025Article
- 25-Hydroxycholesterol modulates microglial function and exacerbates Alzheimer's disease pathology: mechanistic insights and therapeutic potential of cholesterol esterification inhibition.Journal of neuroinflammation · 2025Article
- The Advancements of Marine Natural Products in the Treatment of Alzheimer's Disease: A Study Based on Cell and Animal Experiments.Marine drugs · 2025Review
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.Frontiers in neuroscience · 2025Review
- HDL from 36-h fasted participants potently promotes efflux of cholesteryl ester from activated microglia.Frontiers in aging neuroscience · 2025Article
- Hyperphosphorylated tau targeting human serum albumin Fusion protein as therapeutics for Alzheimer's diseases.IBRO neuroscience reports · 2024Article
- Exosomal mRNA Signatures as Predictive Biomarkers for Risk and Age of Onset in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Lipid Trajectories Improve Risk Models for Alzheimer's Disease and Mild Cognitive Impairment.medRxiv : the preprint server for health sciences · 2024Article
- The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4.bioRxiv : the preprint server for biology · 2024Article
- Brain cholesterol and Alzheimer's disease: challenges and opportunities in probe and drug development.Brain : a journal of neurology · 2024Review
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Preliminary study on early diagnosis of Alzheimer's disease in APP/PS1 transgenic mice using multimodal magnetic resonance imaging.Frontiers in aging neuroscience · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
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Abstract
Patients with Alzheimer's disease (AD) display amyloidopathy and tauopathy. In mouse models of AD, pharmacological inhibition using small molecule enzyme inhibitors or genetic inactivation of acyl-coenzyme A (Acyl-CoA):cholesterol acyltransferase 1 (ACAT1) diminished amyloidopathy and restored cognitive deficits. In microglia, ACAT1 blockage increases autophagosome formation and stimulates amyloid β peptide1-42 degradation. Here, we hypothesize that in neurons ACAT1 blockage augments autophagy and increases autophagy-mediated degradation of P301L-tau protein. We tested this possibility in murine neuroblastoma cells ectopically expressing human tau and in primary neurons isolated from triple transgenic AD mice that express mutant forms of amyloid precursor protein, presenilin-1, and human tau. The results show that ACAT1 blockage increases autophagosome formation and decreases P301L-tau protein content without affecting endogenous mouse tau protein content. In vivo, lacking Acat1 decreases P301L-tau protein content in the brains of young triple transgenic AD mice but not in those of old mice, where extensive hyperphosphorylations and aggregation of P301L-tau take place. These results suggest that, in addition to ameliorating amyloidopathy in both young and old AD mice, ACAT1 blockage may benefit AD by reducing tauopathy at early stage.
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