ArticleBrain : a journal of neurology2021
Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer's disease.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease.Frontiers in molecular neuroscience · 2021Pooled it
- A Systematic Review of the Association between Amyloid-β and τ Pathology with Functional Connectivity Alterations in the Alzheimer Dementia Spectrum Utilizing PET Scan and rsfMRI.Dementia and geriatric cognitive disorders extraPooled it
- Japanese participant data from three gantenerumab trials in early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Long-Term Safety of Gantenerumab in Participants with Alzheimer's Disease: A Phase III, Double-Blind, and Open-Label Extension Study (Marguerite RoAD).Journal of Alzheimer's disease : JAD · 2024Trial
- Amyloid-β PET Radioligands in Alzheimer's Disease: From Plaque Detection to Biomarker-Guided Patient Stratification and Therapeutic Monitoring.Molecular diagnosis & therapy · 2026Review
- Relationships of CSF biomarkers to cortical atrophy in early-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Distinct regional patterns of synaptic vulnerability across hippocampal and parahippocampal subregions in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Extent of Tau and Its Cognitive Implications in Patients With Cerebral Amyloid Angiopathy Without Cognitive Impairment.Neurology · 2026Article
- CSF Proteomic Profiles Associated With White Matter Integrity in Cognitively Normal Older Adults With and Without Amyloid Pathology.Neurology · 2026Article
- Perilesional white matter gradients reveal microstructural differences in cerebral amyloid angiopathy versus Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- Article
- Causal relationships between neuroimaging phenotypes and the risk of early and late-onset alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Hippocampal volume moderates the association between cerebrospinal fluid growth-associated protein 43 and episodic memory performance in older adults.Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition · 2025Article
- Glucose metabolism in hyper-connected regions predicts neurodegeneration and speed of conversion in Alzheimer's disease.European journal of nuclear medicine and molecular imaging · 2025Article
- Evidence for reduced synaptic protein SNAP-25 in cerebrospinal fluid in major depressive disorder and schizophrenia.BMJ mental health · 2025Article
- Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease.Nature communications · 2025Article
- Synapse vulnerability and resilience across the clinical spectrum of dementias.Nature reviews. Neurology · 2025Review
- Synaptic vulnerability to amyloid-β and tau pathologies differentially disrupts emotional and memory neural circuits.Molecular psychiatry · 2025Article
- White matter fractional anisotropy decreases precede hyperintensities in Alzheimer's disease.Cell reports. Medicine · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer's disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer's disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.
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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.