ArticleAlzheimer's research & therapy2021
Association of Aβ deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [
Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Cerebral Volumetric Correlates of Apathy in Alzheimer's Disease and Cognitively Normal Older Adults: Meta-Analysis, Label-Based Review, and Study of an Independent Cohort.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Synaptic Loss in Multiple Sclerosis: A Systematic Review of Human Post-mortem Studies.Frontiers in neurology · 2021Pooled it
- A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Transcranial direct current stimulation and lesions hierarchically reorganize brain network dynamics with biological annotations.Fundamental research · 2026Article
- Distinct regional patterns of synaptic vulnerability across hippocampal and parahippocampal subregions in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Spatial amyloid-informed multimodal brain age as an early marker of Alzheimer's-related vulnerability and risk stratification.The journal of prevention of Alzheimer's disease · 2026Article
- HIV-1 Tat expression drives progressive synaptic decline: evidence from longitudinal [NeuroImmune pharmacology and therapeutics · 2026Article
- Mapping Alzheimer's disease heterogeneity with molecular imaging biomarkers.European journal of clinical investigation · 2026Review
- Cerebrospinal fluid markers link to synaptic plasticity responses and Alzheimer's disease genetic pathways.Molecular neurodegeneration · 2025Article
- Reduced synaptic vesicle protein 2A in extracellular vesicles and brains of Alzheimer's disease: associations with Aβ, tau, synaptic proteins and APOE ε4.Translational neurodegeneration · 2025Article
- An integrated view of the relationships between amyloid, tau, and inflammatory pathophysiology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease.Nature communications · 2025Article
- Associations between fluid biomarkers and PET imaging ([11C]UCB-J) of synaptic pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Synapse vulnerability and resilience across the clinical spectrum of dementias.Nature reviews. Neurology · 2025Review
- Basal forebrain volume is associated with cortical amyloid burden in cognitively unimpaired older adults at varying genetic risk for Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Examining the association between synaptic density and neurofibrillary tau among cognitively impaired and unimpaired older adults with and without Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A: Biomarkers of synaptic density in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Hippocampal subfields: volume, neuropathological vulnerability and cognitive decline in Alzheimer's and Parkinson's disease.Alzheimer's research & therapy · 2025Article
- CHAS infers cell type-specific signatures in bulk brain histone acetylation studies of neurological and psychiatric disorders.Cell reports methods · 2025Article
- Assessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer's disease: a multi-tracer PET study.Alzheimer's research & therapy · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAttempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau).
methodsWe measured SV2A binding ([
resultsWe observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus.
conclusionsOur findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.
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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.