ArticleBrain communications2021
Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer's disease.
Article in Brain communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- Value of blood neural cell-derived small extracellular vesicles in the diagnosis and prediction of Alzheimer's disease: A systematic review.The journal of prevention of Alzheimer's disease · 2025Pooled it
- A Meta-Analysis on Presynaptic Changes in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Pooled it
- Exercise and neural circuit stability in early Alzheimer's disease: evidence across memory, executive, cholinergic, and circadian systems.Frontiers in aging neuroscience · 2026Review
- Differences in inflammatory markers, mitochondrial function, and synaptic proteins in male and female Alzheimer's disease post mortem brains.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Impaired Synaptic Plasticity Mechanisms in Alzheimer's Disease.Metabolic brain disease · 2025Review
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Article
- Future Perspectives of NMDAR in CNS Disorders.Molecules (Basel, Switzerland) · 2025Review
- Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- Selective disruption of synaptic NMDA receptors of the hippocampal trisynaptic circuit in Aβ pathology.Biological research · 2024Article
- Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane.Nature structural & molecular biology · 2023Article
- APP accumulates with presynaptic proteins around amyloid plaques: A role for presynaptic mechanisms in Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Overlap between Central and Peripheral Transcriptomes in Parkinson's Disease but Not Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Disturbance of phylogenetic layer-specific adaptation of human brain gene expression in Alzheimer's disease.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic degeneration has been reported as one of the best pathological correlates of cognitive deficits in Alzheimer's disease. However, the location of these synaptic alterations within hippocampal sub-regions, the vulnerability of the presynaptic versus postsynaptic compartments, and the biological mechanisms for these impairments remain unknown. Here, we performed immunofluorescence labelling of different synaptic proteins in fixed and paraffin-embedded human hippocampal sections and report reduced levels of several presynaptic proteins of the neurotransmitter release machinery (complexin-1, syntaxin-1A, synaptotagmin-1 and synaptogyrin-1) in Alzheimer's disease cases. The deficit was restricted to the outer molecular layer of the dentate gyrus, whereas other hippocampal sub-fields were preserved. Interestingly, standard markers of postsynaptic densities (SH3 and multiple ankyrin repeat domains protein 2) and dendrites (microtubule-associated protein 2) were unaltered, as well as the relative number of granule cells in the dentate gyrus, indicating that the deficit is preferentially presynaptic. Notably, staining for the axonal components, myelin basic protein, SMI-312 and Tau, was unaffected, suggesting that the local presynaptic impairment does not result from axonal loss or alterations of structural proteins of axons. There was no correlation between the reduction in presynaptic proteins in the outer molecular layer and the extent of the amyloid load or of the dystrophic neurites expressing phosphorylated forms of Tau. Altogether, this study highlights the distinctive vulnerability of the outer molecular layer of the dentate gyrus and supports the notion of presynaptic failure in Alzheimer's disease.
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