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 Aβ deposition was present in the cerebral vasculature and, less frequently, in senile plaques. Sequencing of the exons and associated introns 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 of Alzheimer’s disease, the co-presence of paired helical filaments and 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.

Binding of Curcumin to Senile Plaques and Cerebral Amyloid Angiopathy in the Aged Brain of Various Animals and to Neurofibrillary Tangles in Alzheimer's Brain

“…These histopathological features are frequently observed in the aged brains of various nonhuman animal species. SPs and CAA have been observed in the brain of aged nonhuman primates [7,17,21,24], dogs [3,9,16,24,26], cats [18], a camel [19], bears [6,27], a wolverine [22], and a great spotted woodpecker [20], whereas NFTs have been reported only in a chimpanzee [23], sheep [5], bears [6], and a wolverine [22].…”

Beta Amyloid Deposition and Neurofibrillary Tangles Spontaneously Occur in the Brains of Captive Cheetahs (Acinonyx jubatus)

“…27 It has been reported that some animals develop abnormally phosphorylated tau accumulation in neuronal cell bodies, and a recently reported chimpanzee was the first animal diagnosed with tauopathy. 43 As described above, only 2 individual Figure 6. Neuroanatomical distribution of Ab deposits and abnormally phosphorylated tau.…”

“…5 To our knowledge, the presence of Ab deposits and NFTs in the same individual has been detected in only 1 wolverine and 1 chimpanzee. 42,43 Since both of these were only case reports and intracranial infarction or hemorrhage was present in each and may have been the primary lesion responsible for NFTs, it remains unclear whether both findings of AD (NFTs and Ab deposits) spontaneously developed in these cases. Some researchers assume that AD is not present in animals because they do not live long enough to develop this slow-progressing disease.…”

Primate aging in the mammalian scheme: the puzzle of extreme variation in brain aging

“…Primate species differences in neurodegeneration could be sought elsewhere in the APP gene, including the APP promoter (Maloney et al 2004). The tau peptide (MAPT gene) is also 100% identical in humans, chimpanzees, and in few other primates examined (Holzer et al 2004) as discussed in Rosen et al (2008).…”