Joseph A . Knox

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Axonal transport deficits in Alzheimer's disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms(More)
Maintaining DNA integrity is vital for all cells and organisms. Defective DNA repair may contribute to neurological disorders, including Alzheimer's disease (AD). We found reduced levels of BRCA1, but not of other DNA repair factors, in the brains of AD patients and human amyloid precursor protein (hAPP) transgenic mice. Amyloid-β oligomers reduced BRCA1(More)
Diverse lines of evidence suggest that amyloid-β (Aβ) peptides causally contribute to the pathogenesis of Alzheimer disease (AD), the most frequent neurodegenerative disorder. However, the mechanisms by which Aβ impairs neuronal functions remain to be fully elucidated. Previous studies showed that soluble Aβ oligomers interfere with synaptic functions by(More)
Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from(More)
The Rockefeller University Press $30.00 J. Cell Biol. Vol. 209 No. 3 419–433 www.jcb.org/cgi/doi/10.1083/jcb.201407065 JCB 419 Correspondence to Keith A. Vossel: kvossel@gladstone.ucsf.edu; or Lennart Mucke: lmucke@gladstone.ucsf.edu Abbreviations used in this paper: A, amyloid ; AD, Alzheimer’s disease; ANOVA, analysis of variance; [Ca]i, intracellular(More)
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