ArticleThe American journal of pathology2000
Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.
Article in The American journal of pathology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- Population-based neuropathological studies of dementia: design, methods and areas of investigation--a systematic review.BMC neurology · 2006Pooled it
- Clinical, imaging and blood biomarker outcomes in a Phase 3 clinical trial of tau aggregation inhibitor hydromethylthionine mesylate in mild cognitive impairment and mild to moderate dementia due to Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Trial
- Oral Tau Aggregation Inhibitor for Alzheimer's Disease: Design, Progress and Basis for Selection of the 16 mg/day Dose in a Phase 3, Randomized, Placebo-Controlled Trial of Hydromethylthionine Mesylate.The journal of prevention of Alzheimer's disease · 2022Trial
- VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies.International journal of molecular sciences · 2019Trial
- Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.Journal of Alzheimer's disease : JAD · 2018Trial
- Timing matters: early administration of a high-affinity antibody targeting the tau repeat domain prevents aggregation in a mouse tauopathy model.Alzheimer's research & therapy · 2026Article
- High-affinity antibodies specific to the core region of the tau protein exhibit diagnostic and therapeutic potential for Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- P301S-hTau acetylates KEAP1 to trigger synaptic toxicity via inhibiting NRF2/ARE pathway: A novel mechanism underlying hTau-induced synaptic toxicities.Clinical and translational medicine · 2022Article
- Trace Amine Associate Receptor 1 (TAAR1) as a New Target for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2022Article
- The synapse as a treatment avenue for Alzheimer's Disease.Molecular psychiatry · 2022Review
- HMTM-Mediated Enhancement of Brain Bioenergetics in a Mouse Tauopathy Model Is Blocked by Chronic Administration of Rivastigmine.Biomedicines · 2022Article
- Molecular pathology and synaptic loss in primary tauopathies: an 18F-AV-1451 and 11C-UCB-J PET study.Brain : a journal of neurology · 2022Observational
- The propagation mechanisms of extracellular tau in Alzheimer's disease.Journal of neurology · 2022Review
- Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391).Frontiers in neuroscience · 2022Article
- Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer's Disease-Like Experimental Mouse Model.Neural plasticity · 2022Article
- Retina and Brain Display Early and Differential Molecular and Cellular Changes in the 3xTg-AD Mouse Model of Alzheimer's Disease.Molecular neurobiology · 2021Article
- Hsp90 co-chaperones, FKBP52 and Aha1, promote tau pathogenesis in aged wild-type mice.Acta neuropathologica communications · 2021Article
- Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose.Metabolic brain disease · 2021Article
- Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia.The Journal of biological chemistry · 2020Article
- Age-Related Cognitive Impairment: Role of Reduced Synaptobrevin-2 Levels in Deficits of Memory and Synaptic Plasticity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.
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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.