Aged chimpanzees exhibit pathologic hallmarks of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Aβ) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Aβ and tau lesions in brain regions affected by AD in humans. Aβ was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters. Aβ deposition was higher in vessels than in plaques and correlated with increases in tau lesions, suggesting that amyloid build-up in the brain's microvasculature precedes plaque formation in chimpanzees. Age was correlated to greater volumes of Aβ plaques and vessels. Tangle pathology was observed in individuals that exhibited plaques and moderate or severe cerebral amyloid angiopathy, a condition in which amyloid accumulates in the brain's vasculature. Amyloid and tau pathology in aged chimpanzees suggests these AD lesions are not specific to the human brain.

Astrocytic changes with aging and Alzheimer's disease‐type pathology in chimpanzees

“…Soma volume of the PFC GFAP‐ir astrocytes was also significantly larger than in the HC. These results correspond to the pattern of AD‐type pathology that showed a higher total percent area occupied by amyloid plaques as well as greater vascular amyloid deposition in the neocortex compared to the HC (Edler et al, ). Amyloid deposition in the neocortex likely triggered the higher astrogliosis observed in these regions, as activated astrocytes typically surround amyloid plaques (Beach & McGeer, ; Beach et al,1989; DeWitt, Perry, Cohen, Doller, & Silver, ; Duffy et al, ; Kimbrough et al, ; Mancardi et al, ; Mandybur, ; Nagele et al, ; Schechter et al, ; Rodríguez et al, ).…”

“…Examination of the individual AD markers collected by Edler et al () showed that astrocyte density increased with neuritic cluster density ( F 1,16 = 20.9; Figure d), APP/Aβ vessel volume ( F 1,16 = 8.18; Figure e), and Aβ42 vessel volume ( F 1,16 = 9.96, all p 's < .05; Figure f) in the PFC layer I. However, astrocyte density was not associated with APP/Aβ plaque volume or pretangle density (all p 's > .05).…”

“…The processes of these astrocytes extended toward the vasculature in a web‐like fashion (Figure a). Many of these blood vessels were immunoreactive for AD pathology (Figure b,c; Edler et al, ). GFAP‐ir activated astrocytes were also found in association with pretangles and chimpanzee specific neuritic clusters (Figure a,b; Edler et al, ).…”

“…All chimpanzees aged 37 years and older were also included in a recent study of AD pathology in chimpanzees (Edler et al, ). To evaluate the response of astrocytes to the presence of neuropathological changes, the tau, amyloid, and pathology scores were calculated as previously described by Edler et al (). Briefly, the amyloid score was determined using three methods to assess Aβ plaque frequency, progression of amyloid pathology, and staging for cerebral amyloid angiopathy (CAA; Attems, Quass, Jellinger, & Lintner, ; Mirra et al, ; Montine et al, ; Thal et al, ; Vonsattel et al, ).…”

Longevity and sexual maturity vary across species with number of cortical neurons, and humans are no exception

“…Similarly, degenerative disorders such as Alzheimer's dementia that have previously been considered unique to humans might be simply dependent on having enough cortical neurons and thus living long enough to accumulate time‐dependent physiological disruptions and manifest those disorders. Indeed, signs of Alzheimer's disease were recently identified in chimpanzees (Edler et al, ), which have been estimated to have about seven billion cortical neurons (Collins et al, ); it remains to be determined whether this disease also affects other species endowed with large numbers of cortical neurons, and thus long‐lived enough, such as gorillas and orangutans (8–9 billion cortical neurons) and the African elephant (5.6 billion neurons (Herculano‐Houzel et al, ). The field of aging research should thus reconsider the value of absolute time, rather than “metabolic time” or “relative age,” as a key parameter in studies of aging as well as cross‐species comparisons.…”