ArticleBrain structure & function2015
Evidence for Alzheimer's disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons.
Article in Brain structure & function, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 111 citations in OpenAlex.
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Regional juxtacortical microstructural changes and gene expression provide insights into neurodegeneration in Alzheimer's disease.Translational psychiatry · 2026Article
- [Fiber photometry-based analysis of transcranial magneto-acoustic electrical stimulation effects on synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2026Article
- Hypoxia reverses the early anti-inflammatory microglial response to the β-amyloid peptide: mitochondrial involvement and beneficial roles of melatonin and naringenin.Journal of translational medicine · 2025Article
- Potassium homeostasis during disease progression of Alzheimer's disease.The Journal of physiology · 2025Article
- Enhanced prefrontal nicotinic signaling as evidence of active compensation in Alzheimer's disease models.Translational neurodegeneration · 2024Article
- Alzheimer's-linked axonal changes accompany elevated antidromic action potential failure rate in aged mice.Brain research · 2024Article
- Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.iScience · 2024Article
- An aging-sensitive compensatory secretory phospholipase that confers neuroprotection and cognitive resilience.bioRxiv : the preprint server for biology · 2024Article
- Regulation of Hippocamposeptal Synaptic Transmission by GABAJournal of molecular neuroscience : MN · 2024Article
- Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Rodent Models of Alzheimer's Disease: Past Misconceptions and Future Prospects.International journal of molecular sciences · 2024Review
- Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits.Aging cell · 2024Article
- Control of hippocampal synaptic plasticity by microglia-dendrite interactions depends on genetic context in mouse models of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Synaptic Compensatory Plasticity in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- 3D synaptic organization of layer III of the human anterior cingulate and temporopolar cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Advances in proteomic phenotyping of microglia in neurodegeneration.Proteomics · 2023Review
- Article
- CLARITY increases sensitivity and specificity of fluorescence immunostaining in long-term archived human brain tissue.BMC biology · 2023Article
- Genetic context controls early microglia-synaptic interactions in mouse models of Alzheimer's disease.bioRxiv : the preprint server for biology · 2023Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is associated with alterations in the distribution, number, and size of inputs to hippocampal neurons. Some of these changes are thought to be neurodegenerative, whereas others are conceptualized as compensatory, plasticity-like responses, wherein the remaining inputs reactively innervate vulnerable dendritic regions. Here, we provide evidence that the axospinous synapses of human AD cases and mice harboring AD-linked genetic mutations (the 5XFAD line) exhibit both, in the form of synapse loss and compensatory changes in the synapses that remain. Using array tomography, quantitative conventional electron microscopy, immunogold electron microscopy for AMPARs, and whole-cell patch-clamp physiology, we find that hippocampal CA1 pyramidal neurons in transgenic mice are host to an age-related synapse loss in their distal dendrites, and that the remaining synapses express more AMPA-type glutamate receptors. Moreover, the number of axonal boutons that synapse with multiple spines is significantly reduced in the transgenic mice. Through serial section electron microscopic analyses of human hippocampal tissue, we further show that putative compensatory changes in synapse strength are also detectable in axospinous synapses of proximal and distal dendrites in human AD cases, and that their multiple synapse boutons may be more powerful than those in non-cognitively impaired human cases. Such findings are consistent with the notion that the pathophysiology of AD is a multivariate product of both neurodegenerative and neuroplastic processes, which may produce adaptive and/or maladaptive responses in hippocampal synaptic strength and plasticity.
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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.