title: Tauopathy with paired helical filaments in an aged chimpanzee.
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 tau-immunoreactive paired helical filaments with a diameter and helical periodicity indistinguishable from those seen in Alzheimer's disease. A moderate degree of Abeta 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 and Abeta-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.
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Rosen
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Farberg
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Jeromy
authors.initials: J
authors.lastname: Dooyema
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Long
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Anderson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Davis-Turak
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Paré
authors.forename: Timothy Q
authors.initials: TQ
authors.lastname: Duong
authors.forename: William D
authors.initials: WD
authors.lastname: Hopkins
authors.forename: Todd M
authors.initials: TM
authors.lastname: Preuss
authors.forename: Lary C
authors.initials: LC
authors.lastname: Walker
mesh_terms: D016229:Amyloid beta-Peptides / Q000648:ultrastructure; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000648:ultrastructure*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D019600:Neuropil Threads / Q000648:ultrastructure; D002679:Pan troglodytes; D058225:Plaque, Amyloid / Q000648:ultrastructure; D020521:Stroke / Q000473:pathology; D024801:Tauopathies / Q000473:pathology* / Q000662:veterinary*; D016875:tau Proteins / Q000648:ultrastructure
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins