ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Loss of lysosomal acid lipase contributes to Alzheimer's disease pathology and cognitive decline.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026Review
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- INTERFERON-REGULATORY FACTOR 7: A NEUROIMMUNE ROLE FOR VAPOR-INDUCED ESCALATIONS IN ETHANOL SELF-ADMINISTRATION.bioRxiv : the preprint server for biology · 2026Article
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- Loss of lysosomal acid lipase contributes to Alzheimer's disease pathology and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Abstract
introductionUnderlying drivers of Alzheimer's disease (AD) remain unknown, though several distinct risk exposures share a common pathological progression.
methodsThe cellular and molecular consequences of two common midlife AD risk factors-heavy alcohol use and obesity-were compared to uncover novel mediators that contribute to AD.
resultsBoth AD risk exposures reduced levels of neuronal lysosomal acid lipase (LAL), which contributed to AD pathology and cognitive decline. LAL was lost with age in mice and humans with greater losses in AD and inverse associations with amyloid β (Aβ). LAL loss preceded Aβ pathology in AD mice, and neuronal LAL knockdown enhanced pathology and cognitive decline. In human AD brain, robust reductions in LAL protein were found with indications of a transcriptional mechanism. LAL gene therapy reduced pathology and improved cognition and affect in vivo. DISCUSSION: LAL loss is an age-related contributor to AD pathology that can be targeted therapeutically. HIGHLIGHTS: The loss of lysosomal acid lipase (LAL) contributes to Alzheimer's disease progression. LAL is lost is normal aging and Alzheimer's disease risk exposures. LAL loss is greater in human Alzheimer's brain and predicts the extent of pathology. LAL gene therapy blunts Alzheimer' pathology, improving cognition and mood with age.
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