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Synaptic and neuritic alterations during the progression of Alzheimer's disease
Abstract
Extensive synaptic and neuritic alterations in the neocortex and limbic system are characteristically found in Alzheimer's disease (AD). However, it is not known how early in the development of the disease these alterations occur. For the present study, we compared the synaptic and neuritic alterations among cases classified clinically and neuropathologically as early, mild and advanced AD. In early AD there was a 20% loss of synaptophysin-immunoreactive presynaptic terminals in the outer molecular layer of the hippocampal dentate gyrus (but not in the neocortex and entorhinal cortex), accompanied by increased amyloid precursor protein (APP) and Alz50 immunoreactivity in hippocampal and entorhinal cortex pyramidal neurons. These results suggest that abnormal neuronal expression of APP and cytoskeletal proteins in early stages might be involved in the mechanisms of synaptic pathology in AD.
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“which may be a result of our focus on the earliest stages of pathology and/or a dissociation between plaque load and function, which has been observed in other settings.21,60,62”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [21]
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“Remarkably, APP mutant neurons showed differential alterations in synaptic proteins [3] that resembled those that have been described in AD brain, such as early loss of the pre-synaptic protein synaptophysin [113, 163, 192] and the post-synaptic protein PSD-95 [63].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [113]
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Metadata
- Authors
- Masliah, E., Mallory, M., Hansen, L., Richard, D., Alford, M., & Terry, R.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Masliah, Eliezer
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 1994-06
- Volume
- 174
- Issue
- 1
- Pages
- 67-72
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2073518622
- Cited by
- 370
- References
- 30
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 10 · 2023: 17 · 2022: 12 · 2021: 15 · 2020: 19 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 10 · 2015: 14 · 2014: 11 · 2013: 15 · 2012: 18
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag008205-08, 5r01ag008201-05)
- National Institute on Aging (AG 08205, AG05131, P50AG005131, AG08201)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, synaptic pathology, synaptophysin, presynaptic terminals, amyloid precursor protein, amyloid plaques, dentate gyrus, entorhinal cortex, hippocampus, pyramidal neurons, cytoskeletal proteins, disease progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Cerebral Cortex, Cytoskeleton, Hippocampus, Humans, Nerve Tissue Proteins, Synapses, Neurites, Synaptophysin, Pyramidal Cells, Entorhinal Cortex
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