Study identifies gene variants which protect older adults from neurodegeneration.


The standard model of natural selection predicts that once the age of reproduction ends, individuals die. That’s because selection early in life strongly favors variants that benefit reproductive success, even at the cost of negative consequences late in life, one major reason humans age. This is indeed the case in almost all vertebrates. Humans are an exception to this rule, living decades beyond reproductive age; such elders contribute to the fitness of younger individuals by caring for grandchildren and also by passing down important cultural knowledge.

Age-related cognitive decline compromises these benefits, and eventually burdens the group with the need to care for dependent older members.  Now, a study from researchers at the University of California, San Diego School has shown that humans have evolved gene variants that can help protect the elderly from neurodegenerative and cardiovascular diseases, thus preserving their contributions to society.  The team state that these genes likely evolved to preserve valuable and wise elders, as well as to delay or prevent the emergence of dependent individuals who could divert resources and effort away from the care of the young.  The study is published in the journal Proceedings of the National Academy of Sciences.

Previous studies show that a certain form of CD33 suppresses amyloid beta peptide accumulation in the brain. CD33 is a receptor that projects from the surface of immune cells, where it keeps immune reactions in check, preventing ‘self’ attack and curtailing unwanted inflammation.  Amyloid beta accumulation is thought to contribute to late-onset Alzheimer’s disease, a post-reproductive condition that uniquely affects humans and is aggravated by inflammation and cerebral vascular disease.  Therefore, the lab focused on the gene that encodes the CD33 protein in humans and our closest living relatives, chimpanzees. The current study shows that levels of the CD33 variant that protects against Alzheimer’s are four-fold higher in humans than chimpanzees.

The current study shows that human-specific variations in many other genes involved in the prevention of cognitive decline, such as APOE. The group state that the ancestral form of the gene, APOE4, is a notorious risk factor for Alzheimer’s and cerebral vascular disease, however, results show that variants APOE2 and APOE3 seem to have evolved to protect from dementia.

The team surmise that all of these protective gene variants are present in Africa, and thus predate the origin of the human species. For the future, the researchers state that their study does not directly prove that these factors are involved in the selection of protective variants of CD33, APOE and other genes, however, they do denote further investigation.

Source: University of California, San Diego School of Medicine

 

Newly evolved, uniquely human gene variants protect older adults from cognitive decline - neuroinnovations

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