A novel mechanism of memory loss in Alzheimer’s disease mice via the degeneration of entorhinal–CA1 synapses
Open accessAbstract
The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer’s disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECII PN ) directly innervate CA1 parvalbumin (PV) neurons (CA1 PV ) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECII PN –CA1 PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECII PN using a theta burst paradigm rescues ECII PN –CA1 PV synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECII PN –CA1 PV pathway.
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The hippocampal region is important to short-term memory loss in AD and is the earliest region involved in the progression of the disease.
“the hippocampal region is important to short-term memory loss in AD and is the earliest region involved in the progression of the disease”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [42]
The Introduction and Results link hippocampal CA1 circuits to spatial-memory impairment in AD mice, supporting a role for the hippocampal region in memory loss. They do not identify the impairment as short-term memory loss. The Introduction instead identifies entorhinal-cortex neurons as particularly vulnerable early in AD; it does not say the hippocampus is the earliest region involved. (LLM, conf=0.86)
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- Authors
- Yang, X., Yao, C., Tian, T., Li, X., Yan, H., Wu, J., Li, H., Pei, L., Liu, D., Tian, Q., Zhu, L.-Q., & Lu, Y.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Venue
- Molecular Psychiatry
- Published
- 2016-09-27
- Volume
- 23
- Issue
- 2
- Pages
- 199-210
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5794875
- OpenAlex
- W2524076604
- Cited by
- 136
- References
- 62
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 27 · 2021: 23 · 2020: 17 · 2019: 15 · 2018: 10 · 2017: 4 · 2016: 2
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (91232302, 81200863, 31571039, 91132725, 81130079)
- Chinese Academy of Sciences (XDB02050500)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, entorhinal cortex, CA1, parvalbumin interneurons, pyramidal neurons, synaptic degeneration, amyloid plaques, excitation-inhibition balance, spatial learning and memory, optogenetic stimulation, theta burst stimulation, memory loss
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Memory, Memory Disorders, Mice, Transgenic, Neurons, Parvalbumins, Synapses, Presynaptic Terminals, Pyramidal Cells, Entorhinal Cortex, Mice, CA1 Region, Hippocampal, Plaque, Amyloid
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