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Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and α-synuclein pathology

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Abstract

Alzheimer’s disease (AD), Pick’s disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or α-synuclein. In AD, β-amyloid (Aβ)-associated caspase activation and cleavage of tau at Asp421 (ΔTau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether ΔTau accumulates in other diseases not characterized by extracellular Aβ accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we studied ΔTau accumulation in DLB cases associated with intracellular α-synuclein. ΔTau was observed in all disease cases except non-PiD FTLD and controls. These results demonstrate that the accumulation of ΔTau may represent a common pathway associated with abnormal accumulation of intracellular tau or α-synuclein and may be relatively less dependent on the extracellular accumulation of Aβ in non-AD dementias.

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Acknowledgements

This work was supported by NIH/NIA grants R15 AG19642, P20 RR16454 from the BRIN/INBRE Program of the National Center for Research Resources, (T.T.R.), P50 AG16573 (C.W.C.), F32 AG023433 (R.A.R.), and P30 AG10161 (D.A.B.). We also thank Julie Schneider, M.D. (Rush Alzheimer’s Disease Center, Chicago, IL) for neuropathology data and MaryAnn Hill, Ph.D. for statistical consulting.

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Authors and Affiliations

  1. Department of Biology, Boise State University, Boise, Idaho, USA

    Jodie Newman & Troy T. Rohn

  2. Institute for Brain Aging and Dementia, Department of Neurology, University of California, 1259 Gillespie Neuroscience Research Facility, Irvine, CA, 92697, USA

    Robert A. Rissman, Floyd Sarsoza, Ronald C. Kim, Malcolm Dick, Carl W. Cotman & Elizabeth Head

  3. Rush Alzheimer’s Disease Center and Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA

    David A. Bennett

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  1. Jodie Newman
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Correspondence to Elizabeth Head.

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Newman, J., Rissman, R.A., Sarsoza, F. et al. Caspase-cleaved tau accumulation in neurodegenerative diseases associated with tau and α-synuclein pathology. Acta Neuropathol 110, 135–144 (2005). https://doi.org/10.1007/s00401-005-1027-3

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