Journal article
Plaque-Induced Abnormalities in Neurite Geometry in Transgenic Models of Alzheimer Disease: Implications for Neural System Disruption
Journal of neuropathology and experimental neurology, v 60(8), pp 753-758
Aug 2001
PMID: 11487049
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neurites that pass through amyloid-ß deposits in Alzheimer disease (AD) undergo 3 changesthey develop phosphorylated tau immunoreactivity; the density of SMI-32-positive dendrites diminishes; and they also develop a marked alteration in their geometric features, changing from being nearly straight to being quite curvy. The extent to which the latter 2 phenomena are related to phosphorylated tau is unknown. We have now examined whether amyloid-ß deposits in APP695Sw transgenic mice, which have only rare phosphorylated tau containing neurites, develop these changes. We found that dendritic density is diminished within the boundaries of amyloid-ß plaques, with the greatest loss (about 80%, p < 0.001) within the boundaries of thioflavine S cores. Remaining dendrites within plaques develop substantial morphological alterations quantitatively similar to those seen in AD. A statistically significant but smaller degree of change in geometry was seen in the immediate vicinity around plaques, suggesting a propagation of cytoskeletal disruption from the center of the plaque outward. We examined the possible physiological consequences of this change in dendritic geometry using a standard cable-theory model. We found a predicted delay of several milliseconds in about one quarter of the dendrites passing through a thioflavine S plaque. These results are consistent with previous observations in AD, and suggest that thioflavine S-positive amyloid-ß deposits have a marked effect on dendritic microarchitecture in the cortex, even in the relative absence of phosphorylated tau alterations.
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Details
- Title
- Plaque-Induced Abnormalities in Neurite Geometry in Transgenic Models of Alzheimer Disease: Implications for Neural System Disruption
- Creators
- RICKY LE - Department of Neurology (RL, MCI, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; Center for Polymer Studies and Department of Physics (LC, BU, HES), Boston University, Boston, Massachusetts; Department of Biology (RBK), Drew University, Madison, New Jersey; Department of Neurology (KH-A), University of Minnesota, Minneapolis, Minnesota; Dementia Research (KD), Nathan Kline Institute, Orangeburg, New YorkLUIS CRUZBRIGITA URBANCROGER KNOWLESKAREN HSIAO-ASHEKAREN DUFFMICHAEL IRIZARRYH STANLEYBRADLEY HYMAN
- Publication Details
- Journal of neuropathology and experimental neurology, v 60(8), pp 753-758
- Publisher
- American Association of Neuropathologists, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000170192200002
- Scopus ID
- 2-s2.0-0034918436
- Other Identifier
- 991014878003204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pathology