ArticleNature neuroscience2022
Faulty autolysosome acidification in Alzheimer's disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 369 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
369 citing papers in PubMed, 1 synthesis or guideline pooled it, 583 citations in OpenAlex.
- Druggable genome-wide Mendelian randomization identifies therapeutic targets for metabolic dysfunction-associated steatotic liver disease.Lipids in health and disease · 2025Pooled it
- Plant-derived phytochemicals for Alzheimer's disease: mechanisms of action, experimental evidence, and therapeutic perspectives.Journal of natural medicines · 2026Review
- mTORC1 Activation Links Chronic Stress to Meso-Circuit Desynchronization and Accelerated Amyloid Pathology via Autophagic Dysfunction.CNS neuroscience & therapeutics · 2026Article
- The lithium-magnesium-zinc axis under stress: regulation of N-glycosylation-linked proteostasis and Alzheimer's disease.Inflammopharmacology · 2026Review
- Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer's disease.Nature neuroscience · 2026Article
- Site-specific phosphorylation of Ser352 drives aggregation of Tau R4 under acidosis conditions.Chemical science · 2026Article
- Estrogen deprivation exacerbates Alzheimer's disease pathology through neuronal CTSS signaling.Journal of neuroinflammation · 2026Article
- Article
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Neuron-derived SPP1 instructs microglia to limit degeneration.Science advances · 2026Article
- Inhibition of amyloid β aggregation by venetoclax: a computational andRSC advances · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Review
- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- A combined artificial intelligence-wet lab approach identifies a pivotal role of the NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- High reelin expression may explain why a subgroup of entorhinal cortex neurons functions as an initial nucleation site of Alzheimer's disease.PLoS computational biology · 2026Article
- The Glial Autophagy-Lysosomal-Inflammation Axis in Alzheimer's Disease: a Unifying Mechanistic Framework.Molecular neurobiology · 2026Review
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
309 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Autophagy is markedly impaired in Alzheimer's disease (AD). Here we reveal unique autophagy dysregulation within neurons in five AD mouse models in vivo and identify its basis using a neuron-specific transgenic mRFP-eGFP-LC3 probe of autophagy and pH, multiplex confocal imaging and correlative light electron microscopy. Autolysosome acidification declines in neurons well before extracellular amyloid deposition, associated with markedly lowered vATPase activity and build-up of Aβ/APP-βCTF selectively within enlarged de-acidified autolysosomes. In more compromised yet still intact neurons, profuse Aβ-positive autophagic vacuoles (AVs) pack into large membrane blebs forming flower-like perikaryal rosettes. This unique pattern, termed PANTHOS (poisonous anthos (flower)), is also present in AD brains. Additional AVs coalesce into peri-nuclear networks of membrane tubules where fibrillar β-amyloid accumulates intraluminally. Lysosomal membrane permeabilization, cathepsin release and lysosomal cell death ensue, accompanied by microglial invasion. Quantitative analyses confirm that individual neurons exhibiting PANTHOS are the principal source of senile plaques in amyloid precursor protein AD models.
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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.