Why Are Humans Vulnerable to Alzheimer’s Disease?

Abstract

Since Alzheimer’s disease (AD) is harmful, it is somewhat of a mystery as to why it hasn’t been eliminated by natural selection. Typically, AD has been thought to be “invisible” to natural selection because people have already passed on their genes by the time that AD manifests (usually after age 65). But, this hypothesis may not tell the whole story. One possible explanation is that since the E4 form of the APOE gene, a strong risk gene for AD, is very similar to that of our ape-like ancestors but is not currently the most common form in humans, it may have been selected against by natural selection. In addition, as humans take care of their extended family (who shares their genes) even when they are no longer able to have children themselves, the ability to remain cognitively functional in old age may have been selected for. A second possibility is that AD exists in humans because it is the inevitable cost of other features that are beneficial to us—our highly neuroplastic brains, for example. If the benefits outweigh the costs, AD may be maintained despite the severe disadvantages experienced by the elderly. Finally, a third consideration about AD is that it is common due to the mismatch between the environment and lifestyle humans typically sustained during their evolutionary history and the contemporary post-industrialized environment, characterized by high-calorie diets, sedentary lifestyle, and a shortage of pathogens (resulting in autoimmune dysfunction) An evolutionary approach has implications for rethinking the biological hallmarks of AD. The brains of AD patients have two characteristic signs— abnormal accumulations of a protein called amyloid-β into “plaques” between brain cells and accumulation of abnormal tau protein into “tangles” inside neurons. These lesions are commonly thought to be the cause of neuron death in AD, but there is no direct evidence for this in humans. To date, experi- mental drugs that have targeted plaques have been ineffective and some have hastened the disease. There is a possibility that plaques and tangles may be harmless by-products of the actual destructive processes, or might even serve an adaptive function, such as trapping free-floating amyloid-β in the brain or protecting against a natural but harmful bodily process called oxidative stress. If this is the case, care should be taken when developing clinical therapies, because interrupting one of the body’s beneficial responses may make symptoms worse rather than better.