Re-Evaluation of the Structural Organization of Neuritic Plaques in Alzheimerʼs Disease
Abstract
We re-examined the relationship among synaptic pathology, subcellular abnormalities within neurites in the plaques and beta-amyloid deposits of Alzheimer's disease (AD) using laser confocal imaging and computer-aided serial section reconstruction techniques. Analysis of serial optical sections of neuritic plaques double-immunolabeled for anti-beta-amyloid/anti-tau-2 revealed that 35% of this type of plaque contained a dense amyloid core with clusters of peripheral abnormal neurites. The other 65% were without a dense core and were mainly composed of abundant abnormal neuritic clusters with bundles of amyloid distributed throughout the neuritic plaque. While two-dimensional (2-D) analysis of the plaques has suggested that neurites are distributed in the plaque periphery with beta-amyloid localized in its center, serial section analysis showed the opposite arrangement can also be true. Three-dimensional (3-D) reconstructions of serial optical sections showed that the tau-positive tortuous axons clustered in the neuritic plaques were often continuous with synaptophysin-positive distended terminals. Analysis of electron micrographs from serial sections showed continuity among the different segments of the neurites. Further analysis of the computer generated 3-D reconstructed neuritic plaques (both from serial electron micrographs and serial optical sections), viewed as continuous rotating loops, confirmed that a great majority of the plaque volume was occupied by the clustered an…
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Neuritic plaques appear closely associated with neuronal injury and are characterized by dystrophic neurites that frequently have phospho-tau immunoreactivity.
“A subset of senile plaques called neuritic plaques appear closely associated with neuronal injury and are characterized by the occurrence of dystrophic neurites that frequently have phospho-tau immunoreactivity [19,36,37,55].”
From National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach (2012) · cites this paper as [36]
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- Authors
- MASLIAH, E., MALLORY, M., DEERINCK, T., DETERESA, R., LAMONT, S., MILLER, A., TERRY, R. D., CARRAGHER, B., & ELLISMAN, M.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- MASLIAH, ELIEZER
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-11
- Volume
- 52
- Issue
- 6
- Pages
- 619-632
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2003632380
- Cited by
- 105
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2013: 2 · 2012: 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neuritic plaques, Alzheimer's disease, amyloid-beta, tau protein, synaptic pathology, amyloid core, synaptophysin, axons, 3D reconstruction, serial section imaging
- MeSH terms
- Aged, Alzheimer Disease, Cerebral Cortex, Diagnosis, Computer-Assisted, Humans, Immunohistochemistry, Microscopy, Electron, Synapses, Amyloid beta-Peptides, Neurites, Synaptophysin, tau Proteins
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