ArticleMolecular psychiatry2018
Synaptic activity protects against AD and FTD-like pathology via autophagic-lysosomal degradation.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Deep brain stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis.Frontiers in neuroscience · 2023Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Scalable human neuronal models of tauopathy producing endogenous seed-competent 4R tau.Science advances · 2026Article
- Neuronal activity and amyloid-β promote tau seeding in the entorhinal cortex in Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Presenilin-dependent regulation of neuronal tau pathology via the autophagy and proteasome pathways.Acta neuropathologica communications · 2026Article
- Exploring the PLD1-tau interaction in Frontotemporal Dementia.bioRxiv : the preprint server for biology · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Optogenetic regulation of chloride ions in reactive astrocytes may mitigate Parkinson's disease pathology.Scientific reports · 2025Article
- Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- The Role of Oligodendrocyte Lineage Cells in the Pathogenesis of Alzheimer's Disease.Neurochemical research · 2025Review
- Multi-path direct current spinal stimulation extended survival in the SOD1-G93A model of amyotrophic lateral sclerosis.Frontiers in neurology · 2025Article
- Autophagy in alzheimer disease pathogenesis and its therapeutic values.Autophagy reports · 2025Review
- Deep Brain Stimulation Combined with NMDA Antagonist Therapy in the Treatment of Alzheimer's Disease: In Silico Trials.Journal of clinical medicine · 2024Article
- Synaptopathy: presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Review
- Activity-dependent mechanisms of neuroprotection: promising avenues against dementia.Neural regeneration research · 2024Article
- Targeting papez circuit for cognitive dysfunction- insights into deep brain stimulation for Alzheimer's disease.Heliyon · 2024Review
- The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms.Aging and disease · 2024Review
- Review
- Stimulation of synaptic activity promotes TFEB-mediated clearance of pathological MAPT/Tau in cellular and mouse models of tauopathies.Autophagy · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 5 countries.
Funding
Abstract
Changes in synaptic excitability and reduced brain metabolism are among the earliest detectable alterations associated with the development of Alzheimer's disease (AD). Stimulation of synaptic activity has been shown to be protective in models of AD beta-amyloidosis. Remarkably, deep brain stimulation (DBS) provides beneficial effects in AD patients, and represents an important therapeutic approach against AD and other forms of dementia. While several studies have explored the effect of synaptic activation on beta-amyloid, little is known about Tau protein. In this study, we investigated the effect of synaptic stimulation on Tau pathology and synapses in in vivo and in vitro models of AD and frontotemporal dementia (FTD). We found that chronic DBS or chemically induced synaptic stimulation reduced accumulation of pathological forms of Tau and protected synapses, while chronic inhibition of synaptic activity worsened Tau pathology and caused detrimental effects on pre- and post-synaptic markers, suggesting that synapses are affected. Interestingly, degradation via the proteasomal system was not involved in the reduction of pathological Tau during stimulation. In contrast, chronic synaptic activation promoted clearance of Tau oligomers by autophagosomes and lysosomes. Chronic inhibition of synaptic activity resulted in opposite outcomes, with build-up of Tau oligomers in enlarged auto-lysosomes. Our data indicate that synaptic activity counteracts the negative effects of Tau in AD and FTD by acting on autophagy, providing a rationale for therapeutic use of DBS and synaptic stimulation in tauopathies.
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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.