Dystrophic peptidergic neurites in senile plaques of Alzheimer's disease hippocampus precede formation of paired helical filaments
Abstract
The relationship between peptidergic dystrophic neurites and paired helical filament (PHF)-positive neurites in Alzheimer's disease (AD) senile plaques (SPs) was studied using combined fluorescence and bright-field optics. Cryostat sections of AD hippocampi were first stained with thioflavine-S and immunolabelled with antisera raised against different neuropeptides: somatostatin-28(1-12), somatostatin-14, neuropeptide Y, cholecystokinin (CCK) and substance P. Secondly, using the elution-restaining procedure, sections were immunolabelled with anti-tau/PHF. In immature SPs, clusters of abnormal, swollen neurites were found. The dystrophic, strongly peptidic-positive neurites contained fewer PHFs than the poorly positive ones. Cell bodies, exhibiting a peptidic content, could be found within SPs without any alteration. These results suggest the following sequence of events: an extracellular poisoning mechanism, perhaps the amyloid substance, first changes the structure of presynaptic endings and causes the formation of ballooning dystrophic neurites filled with their normal peptidic content. Subsequently, intracellular degradation occurs with formation of the PHFs. Then the other structures such as dendrites and perikarya are damaged by the same mechanism. Therefore, this phenomenon seems to precede any formation of PHFs in SPs.
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NPs represent a nidus in which extracellular plaque substance(s) seem to induce intracellular degenerative changes with tau pathology.
“The particular toxic substance(s) within NPs still have not been completely characterized (90, 103, 278), but NPs represent a nidus in which extracellular plaque substance(s) seem to induce intracellular degenerative changes with tau pathology (18, 50, 279-281).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [281]
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- Authors
- Lenders, M.-B., Peers, M.-C., Tramu, G., Delacourte, A., Defossez, A., Petit, H., & Mazzuca, M.
- Affiliations
- Centre Hospitalier Universitaire de Lille (FR)
- Inserm (FR)
- Corresponding author
- Delacourte, André
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1989-03
- Volume
- 481
- Issue
- 2
- Pages
- 344-349
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2056895835
- Cited by
- 27
- References
- 34
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2012: 2
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- 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
- Alzheimer's disease, amyloid plaques, paired helical filaments, dystrophic neurites, hippocampus, somatostatin, neuropeptide Y, cholecystokinin, substance P, tau protein, amyloid, pathogenesis
- MeSH terms
- Alzheimer Disease, Cytoskeleton, Dendrites, Hippocampus, Humans, Immunohistochemistry, Intermediate Filaments, Microtubule-Associated Proteins, Neuropeptides, tau Proteins
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