Tauopathy with paired helical filaments in an aged chimpanzee

Rebecca F. Rosen, Aaron S. Farberg, Marla Gearing, Jeromy Dooyema, Patrick M. Long, Daniel C. Anderson, Jeremy Davis-Turak, Giovanni Coppola, Daniel H. Geschwind, Jean Francois Paré, Timothy Q. Duong, William D. Hopkins, Todd M. Preuss, Lary C. Walker

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

An enigmatic feature of age-related neurodegenerative diseases is that they seldom, if ever, are fully manifested in nonhuman species under natural conditions. The neurodegenerative tauopathies are typified by the intracellular aggregation of hyperphosphorylated microtubule-associated protein tau (MAPT) and the dysfunction and death of affected neurons. We document the first case of tauopathy with paired helical filaments in an aged chimpanzee (Pan troglodytes). Pathologic forms of tau in neuronal somata, neuropil threads, and plaque-like clusters of neurites were histologically identified throughout the neocortex and, to a lesser degree, in allocortical and subcortical structures. Ultrastructurally, the neurofibrillary tangles consisted of tauimmunoreactive paired helical filaments with a diameter and helical periodicity indistinguishable from those seen in Alzheimer's disease. A moderate degree deposition was present in the cerebral vasculature and, less frequently, in senile plaques. Sequencing of the exons and flanking intronic regions in the genomic MAPT locus disclosed no mutations that are associated with the known human hereditary tauopathies, nor any polymorphisms of obvious functional significance. Although the lesion profile in this chimpanzee differed somewhat from that in Alzheimer's disease, the copresence of paired helical filaments Aβ-amyloidosis indicates that the molecular mechanisms for the pathogenesis of the two canonical Alzheimer lesions - neurofibrillary tangles and senile plaques - are present in aged chimpanzees.

Original languageEnglish (US)
Pages (from-to)259-270
Number of pages12
JournalJournal of Comparative Neurology
Volume509
Issue number3
DOIs
StatePublished - Jul 20 2008

Keywords

  • Aging
  • Alzheimer's disease
  • Amyloid
  • Cerebral amyloid angiopathy
  • Neurodegeneration
  • Neurofibrillary tangles
  • Pan troglodytes
  • Proteopathy
  • Senile plaques
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)

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    Rosen, R. F., Farberg, A. S., Gearing, M., Dooyema, J., Long, P. M., Anderson, D. C., Davis-Turak, J., Coppola, G., Geschwind, D. H., Paré, J. F., Duong, T. Q., Hopkins, W. D., Preuss, T. M., & Walker, L. C. (2008). Tauopathy with paired helical filaments in an aged chimpanzee. Journal of Comparative Neurology, 509(3), 259-270. https://doi.org/10.1002/cne.21744