Cited by 374Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

Synaptic and neuritic alterations during the progression of Alzheimer's disease

Masliah, Eliezer, Mallory, Margaret, Hansen, Lawrence, Richard, DeTeresa, Alford, Michael, Terry, Robert·1994·Neuroscience Letters

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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Crossref · 10.1016/0304-3940(94)90121-x

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  • The inability to associate altered pathology with detectable changes in brain function may be a result of the focus on the earliest stages of pathology and/or a dissociation between plaque load and function.

    “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”
  • APP mutant neurons show differential alterations in synaptic proteins resembling those in AD brain, including early loss of synaptophysin and PSD-95.

    “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].”

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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
  • Health Sciences › Medicine › Physiology › 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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