Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease
Abstract
Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigated the relationship between synaptic and dendritic abnormalities in the neocortex of Alzheimer patients and examined the extent to which these structural alterations correlate with the severity of cognitive impairment in AD. Quantitative neuroanatomical data were obtained from immunofluorescence-labeled specimens using a laser-scanning confocal microscope, computer-assisted image processing and serial section reconstruction techniques. We found that the AD cases showed a 34% loss in the number of presynaptic terminals per 100 square (sq) microns, many of which showed structural abnormalities. The AD neuropil had an average of 10 +/- 7 dendritic threads per 1,000 sq microns, with the average thread measuring 2 sq microns. Severe AD cases had thicker threads compared with mild to moderate AD cases. Three-dimensional analysis showed clustering of synapses around threads, as well as presynaptic boutons apposed to dendritic neuropil threads. Statistical analysis showed that the strongest correlation was between synapse density and Blessed score of cognitive impairment. Thread counts did not correlate with either but were correlated with tangle counts. Stepwise multipl…
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There are studies suggesting a strong correlation between the loss of synaptic markers and the presence of neurofibrillary tangles.
“Indeed, there are studies suggesting a strong correlation between the loss of synaptic markers and the presence of neurofibrillary tangles (Terry et al., 1991; Honer et al., 1992; Masliah et al., 1992; Wakabayashi et al., 1994; Lue et al., 1996; Samuel et al., 1997; Heffernan et al., 1998).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Masliah et al., 1992
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- Authors
- Masliah, E., Ellisman, M., Carragher, B., Mallory, M., Young, S., Hansen, L., Deteresa, R., & Terry, R. D.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Masliah, E
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1992-07
- Volume
- 51
- Issue
- 4
- Pages
- 404-414
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2032687897
- Cited by
- 183
- References
- 0
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 7 · 2012: 1
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 08205, AG05131, P50AG005131, R01AG008205, AG08201, R01AG008201)
- 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, neuropil threads, presynaptic terminals, synaptic density, neurofibrillary tangles, dendritic cytoskeleton, cognitive impairment, neocortex
- MeSH terms
- Aged, Alzheimer Disease, Dendrites, Humans, Image Processing, Computer-Assisted, Lasers, Middle Aged, Nerve Net, Synapses
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