Chimpanzees have Alzheimer’s neuropathology including plaques and tangles

Many articles include the premise that Alzheimer’s disease (AD) neuropathology is unique to humans. However, there is a large body of literature suggesting that the characteristic neuropathology of AD, including diffuse amyloid plaques, neuritic amyloid plaques, and abnormally phosphorylated tau, are also seen in some non-human primates.

One of the only exceptions where AD pathology has not been commonly reported is coexisting amyloid plaques and neurofibrillary tangles, although even this has been reported in one chimpanzee.

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Coexisting tau and amyloid immunoreactivity in the PFC of a 41-year old chimpanzee; PMC2573460

On the genetic level, tau is identical between chimps and humans, while APP is 99% identical.

It is not that surprising that chimps would have the most similar neuropathology as humans, because chimps (and bonobos) are among the most similar non-human primates to humans.

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cladogram based on morphology and genetics from http://anthro.palomar.edu/primate/prim_8.htm

Now, a nice article from Edler et al examines neuropathology from 20 chimpanzees aged 37-62 to directly interrogate the presence of AD neuropathology in a large sample.

The authors scored neuropathology in all 20 chimpanzees in 4 brain regions (PFC, MTG, CA1, CA3) using the following scoring system:

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Here were some of their findings:

  • All of the chimps had APP/Aβ and Aβ-positive blood vessels, while only 2/3rds had plaques not associated with vessels, suggested that Aβ accumulation near blood vessels may be an early or precursor lesion in chimps.
  • Cerebral amyloid angiopathy, which is seen in 80% of AD patients, had a strong association with tau pathology in their chimps, especially pretangle density:
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CAA = Cerebral Amyloid Angiopathy; Fig 7B; PMID: 28888720
  • On the other hand, Aβ42 levels were not correlated with tau pathology.
  • Pretangle and NFT staining in chimps followed the pattern of Braak staging seen in humans.
  • In reviewing the literature, they note that only subtle, but not profound, age-related memory decline has been demonstrated in chimps. This may be because chimps have differences in APOE and other factors, but it is also the case that very few studies have directly addressed this question.

Overall, the most important finding from this study confirmed the previous 2008 report from a single chimp that amyloid and tau can coexist species other than humans.

These non-human primate studies shine an important light on the true biology of AD, which is especially important to consider when evolutionary or environmental explanations are invoked to explain the disease.