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Tauopathy with paired helical filaments in an aged chimpanzee
Rebecca F Rosen1, Aaron S Farberg, Marla Gearing
1Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA.
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.
Insights
Researchers identified the first case of tauopathy, a brain disease, in an aged chimpanzee. This finding suggests that the molecular mechanisms underlying Alzheimer
Area of Science:
- Neuroscience
- Primatology
- Pathology
Background:
- Age-related neurodegenerative diseases, particularly tauopathies, are characterized by the accumulation of hyperphosphorylated tau protein (MAPT) leading to neuronal dysfunction and death.
- These diseases are rarely observed in nonhuman species under natural conditions, making comparative studies challenging.
- Tauopathies involve the intracellular aggregation of tau protein, forming neurofibrillary tangles.
Observation:
- The study documents the first confirmed case of tauopathy with paired helical filaments in an aged chimpanzee (Pan troglodytes).
- Pathological tau aggregates were identified in various brain regions, including the neocortex, allocortex, and subcortical structures.
- Ultrastructural analysis revealed neurofibrillary tangles composed of tau-immunoreactive paired helical filaments, indistinguishable from those in human Alzheimer's disease.
Findings:
- The chimpanzee exhibited tau pathology alongside moderate Abeta deposition in cerebral vasculature and senile plaques.
- Genetic analysis of the MAPT locus revealed no mutations associated with human hereditary tauopathies.
- The presence of paired helical filaments and Abeta-amyloidosis indicates shared molecular pathogenesis mechanisms with Alzheimer's disease.
Implications:
- This case provides crucial insights into the potential for tauopathy development in nonhuman primates.
- Aged chimpanzees may serve as a valuable model for studying the molecular mechanisms of neurodegenerative diseases like Alzheimer's.
- Understanding these shared pathways can advance research into potential therapeutic strategies for human tauopathies.
