TY - JOUR
T1 - Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease
T2 - Implications for neural system disruption
AU - Le, Ricky
AU - Cruz, Luis
AU - Urbanc, Brigita
AU - Knowles, Roger B.
AU - Hsiao-Ashe, Karen
AU - Duff, Karen
AU - Irizarry, Michael C.
AU - Stanley, H. Eugene
AU - Hyman, Bradley T.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Neurites that pass through amyloid-β deposits in Alzheimer disease (AD) undergo 3 changes: they 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-β 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-β 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-β deposits have a marked effect on dendritic microarchitecture in the cortex, even in the relative absence of phosphorylated tau alterations.
AB - Neurites that pass through amyloid-β deposits in Alzheimer disease (AD) undergo 3 changes: they 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-β 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-β 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-β deposits have a marked effect on dendritic microarchitecture in the cortex, even in the relative absence of phosphorylated tau alterations.
KW - Alzheimer disease
KW - Modeling
KW - Neural networks
KW - Senile plaque
KW - Transgenic
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U2 - 10.1093/jnen/60.8.753
DO - 10.1093/jnen/60.8.753
M3 - Article
C2 - 11487049
AN - SCOPUS:0034918436
VL - 60
SP - 753
EP - 758
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 8
ER -