ArticleCell reports2018
Altered γ-Secretase Processing of APP Disrupts Lysosome and Autophagosome Function in Monogenic Alzheimer's Disease.
Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Review
- SORL1 variant links endosomal amyloid precursor protein mis-sorting to axonal transport defects and neuronal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Neurodegenerative NMNAT2 Deficiency Promotes APP Processing in a SARM1-Dependent Manner.Cells · 2026Article
- Functional relationships linking C99/APP-βCTF dimerization, proteostasis disruption, and organelle dysfunction.Cell communication and signaling : CCS · 2026Article
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- A C. elegans model of familial Alzheimer's disease shows age-dependent synaptic degeneration independent of amyloid β-peptide.Neurobiology of disease · 2026Article
- Lysosomal protease-mediated APP degradation is pH-dependent, mutation-sensitive, and facilitates tau proteolysis.Molecular neurodegeneration advances · 2026Article
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes.Cell death & disease · 2025Article
- Identification of presenilin mutations that have sufficient gamma-secretase proteolytic activity to mediate Notch signaling but disrupt organelle and neuronal health.Neurobiology of disease · 2025Article
- Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Presenilin, γ-Secretase, and the Search for Pathogenic Triggers of Alzheimer's Disease.Biochemistry · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Organelle perturbation in Alzheimer's disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?Frontiers in cell and developmental biology · 2025Review
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.Journal of extracellular vesicles · 2025Article
- Clearance of beta-amyloid and tau aggregates is size dependent and altered by an inflammatory challenge.Brain communications · 2025Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Abnormalities of the endolysosomal and autophagy systems are found in Alzheimer's disease, but it is not clear whether defects in these systems are a cause or consequence of degenerative processes in the disease. In human neuronal models of monogenic Alzheimer's disease, APP and PSEN1 mutations disrupt lysosome function and autophagy, leading to impaired lysosomal proteolysis and defective autophagosome clearance. Processing of APP by γ-secretase is central to the pathogenic changes in the lysosome-autophagy system caused by PSEN1 and APP mutations: reducing production of C-terminal APP by inhibition of BACE1 rescued these phenotypes in both APP and PSEN1 mutant neurons, whereas inhibition of γ-secretase induced lysosomal and autophagic pathology in healthy neurons. Defects in lysosomes and autophagy due to PSEN1 mutations are rescued by CRISPR-knockout of APP. These data demonstrate a key role for proteolysis of the C-terminal of APP by γ-secretase in neuronal dysfunction in monogenic Alzheimer's disease.
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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.