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Journal of Neuroscience, Vol 13, 508-515, Copyright © 1993 by Society for Neuroscience
Functional studies of Alzheimer's disease tau protein
Q Lu and JG Wood
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.
In vitro assays were used to monitor and compare the kinetic behavior of
bovine tubulin polymerization enhanced by tau proteins isolated from
Alzheimer's disease (AD) and nondemented (ND) age-matched control brains.
Tau from AD cases induced slower polymerization and a steady state
turbidity value approximately 50% of that stimulated by tau from control
cases. Tau from the most severe AD case was least effective at promoting
polymerization. Dark-field light microscopy of the control samples revealed
abundant microtubule formation and many microtubule bundles. Microtubule
assembly was observed in AD samples as well, but bundling was not obvious.
These results were confirmed by negative- stain electron microscopy.
Morphological analysis showed that AD tau- induced microtubules were longer
than control microtubules. Furthermore, our initial results suggest that
the reduction of AD tau activity is correlated with neurofibrillary
pathology in AD brains. Earlier reports indicated that AD tau is modified
by phosphorylation (Grundke-Iqbal et al., 1986; Wood et al., 1986; Iqbal et
al., 1989; Brion et al., 1991a,b; Lee et al., 1991). Our results support
the hypothesis that tau modification compromises its function by altering
its ability to nucleate and bundle microtubules.
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