Aβ Associated Neuropil Changes: Correlation with Neuronal Loss and Dementia
Abstract
Although genetic studies clearly implicate beta-amyloid peptide (Abeta) as a pathogenic agent in Alzheimer disease (AD), it is puzzling that the total amount of Abeta immunoreactivity does not correlate closely with neuronal loss or degree of dementia. We hypothesized that Abeta deposits could vary in the extent to which they disrupt the neuropil, and that the degree to which this occurs might then correlate with the degree of dementia. We used 3 dimensional triple immunofluorescent confocal microscopy to examine the fine structural relationships between Abeta deposits and neurites in their vicinity. In non-demented elderly, Abeta deposits were porous structures with numerous normal appearing processes coursing through them. In AD, dendrites within Abeta deposits, compared with dendrites in the surrounding neuropil, were likely to have decreased SMI32 immunoreactivity and increased Alz-50 immunoreactivity. We found that the degree to which Abeta deposits disrupt the neuropil, as assessed by local loss of SMI32 immunoreactivity, correlates closely with the amount of neuronal loss and with duration of dementia. These observations support the hypothesis that a subset of Abeta deposits contribute directly to neural system failure in AD.
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The density of dendrites is diminished within the space occupied by a plaque.
“Although there is no doubt that the density of dendrites is diminished within the space occupied by a plaque (Knowles et al., 1998)”
From Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005) · cites this paper as Knowles et al., 1998
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Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Spires, T. L., Meyer-Luehmann, M., Stern, E. A., McLean, P. J., Skoch, J., Nguyen, P. T., Bacskai, B. J., & Hyman, B. T. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1879-05.2005 · Cited by 550 · see citing works
“Although there is no doubt that the density of dendrites is diminished within the space occupied by a plaque (Knowles et al., 1998), the density of ascending dendrites is not diminished above plaques, arguing against widespread breakage of dendrites in the neocortex.”
BackgroundSelf-citationUrbanc, B., Cruz, L., Le, R., Sanders, J., Ashe, K. H., Duff, K., Stanley, H. E., Irizarry, M. C., & Hyman, B. T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222433299 · Cited by 237 · see citing works
Self-citationBondolfi, L., Calhoun, M., Ermini, F., Kuhn, H. G., Wiederhold, K.-H., Walker, L., Staufenbiel, M., & Jucker, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00515.2002 · Cited by 213 · see citing works
Cortical Synaptic Integration<i>In Vivo</i>Is Disrupted by Amyloid-β Plaques
Stern, E. A., Bacskai, B. J., Hickey, G. A., Attenello, F. J., Lombardo, J. A., & Hyman, B. T. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0462-04.2004 · Cited by 210 · see citing works
Self-citationImpaired Spine Stability Underlies Plaque-Related Spine Loss in an Alzheimer's Disease Mouse Model
Spires-Jones, T. L., Meyer-Luehmann, M., Osetek, J. D., Jones, P. B., Stern, E. A., Bacskai, B. J., & Hyman, B. T. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070055 · Cited by 189 · see citing works
Self-citationAmyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations
Lombardo, J. A., Stern, E. A., McLellan, M. E., Kajdasz, S. T., Hickey, G. A., Bacskai, B. J., & Hyman, B. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10879.2003 · Cited by 149 · see citing works
Self-citationMucke, L., Yu, G.-Q., McConlogue, L., Rockenstein, E. M., Abraham, C. R., & Masliah, E. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64839-0 · Cited by 145 · see citing works
- Authors
- KNOWLES, R. B., GOMEZ-ISLA, T., & HYMAN, B. T.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- HYMAN, BRADLEY T.
- ORCID
- HYMAN, BRADLEY T.
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-12
- Volume
- 57
- Issue
- 12
- Pages
- 1122-1130
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W1973601487
- Cited by
- 79
- References
- 0
- Citations by year
- 2024: 5 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2017: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-08487, P50AG005134, AG 05134)
- 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
- beta-amyloid deposits, Alzheimer's disease, dendrites, neuronal loss, amyloid pathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dendrites, Humans, Immunohistochemistry, Neurons, Linear Models, Case-Control Studies, Amyloid beta-Peptides, Neurites, Neurofibrillary Tangles, Cell Death, Neuropil
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