Saturday, December 05, 2015

Human Unique Genes may Protect From Dementia

Many human gene variants have evolved specifically to protect older adults against neurodegenerative and cardiovascular diseases, thus preserving their contributions to society, report University of California, San Diego School of Medicine researchers in the November 30 issue of Proceedings of the National Academy of Sciences.

"We unexpectedly discovered that humans have evolved gene variants that can help protect the elderly from dementia," said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, adjunct professor at the Salk Institute for Biological Studies and co-director of the UC San Diego/Salk Center for Academic Research and Training in Anthropogeny (CARTA). "Such genes likely evolved to preserve valuable and wise grandmothers and other 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." Varki led the study, along with Pascal Gagneux, PhD, associate professor of pathology and associate director of CARTA.

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 we age. This is indeed the case in almost all vertebrates. Humans (and certain whales) 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.

In this first-of-its kind discovery, Varki, Gagneux and their teams initially focused on the gene that encodes the CD33 protein. 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. Previous studies suggested that a certain form of CD33 suppresses amyloid beta peptide accumulation in the brain. 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.

The researchers compared CD33 regulation in humans and our closest living relatives, chimpanzees. They found that levels of the CD33 variant that protects against Alzheimer's are four-fold higher in humans than chimpanzees.

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