Of the millions of animals on Earth, including the relativehandful that are considered the most intelligent — including apes, whales,crows, and owls — only humans experience the severe age-related decline inmental abilities marked by Alzheimer’sdisease.To BruceYankner, professor of pathology and neurology at Harvard Medical School (HMS),it’s pretty clear that evolution is to blame.“Something has occurred in evolution that makes our brainsusceptible to age-related change,” Yankner said in a talk last nightsponsored by the HarvardMuseum of Natural History as part of its “EvolutionMatters” lecture series.Yankner, whose HMS lab studies brain aging and how gettingold gives rise to the pathology of Alzheimer’s and Parkinson’s diseases, said Alzheimer’s isone of the most rapidly emerging diseases of this century. As medical sciencelengthens human lifespan, the proportion of the population that is elderly isgrowing. Considering that as many as half of those over age 85 developAlzheimer’s, there is a growing urgency to understand the disease more fullyand to develop more effective interventions.“It is clear that cognitive impairment and decline is one ofthe emerging health threats of the 21st century,” Yankner said.Yankner said that scientific evidence shows that somecognitive decline — beginning in middle age and accelerating after age 70 — isnormal as we grow older. This decline is also seen in other animals, includingmice and monkeys. It is marked by wide variation among individuals, with someindividuals maintaining cognitive abilities similar to those much younger.The puzzling question, Yankner said, is why humans developthe severe disabilities of Alzheimer’s disease. Studies of other creatures showno sign of similar conditions even in our closest animal relatives. That meanssusceptibility to Alzheimer’s evolved recently, likely during a period markedby a rapid increase in our brain size. Size alone probably isn’t thedetermining factor, though, Yankner said, since other animals are known to haveeven larger brains, including whales, elephants, and even our extinct relativethe Neanderthal.Instead, he said, it is likely that brain complexity and thenew large number of cells in the human brain have something to do with it.Recent research, in Yankner’s lab and elsewhere, has usedgenetic tools to probe the differences between young and old brains in humans,monkeys, and mice. The work shows that gene function in the aging brain slows —dramatically in ones with Alzheimer’s — and that the genes that shut off themost are those that protect the brain against genetic damage from environmentaland other factors.Yankner said he believes that cognitive decline is due to aslow accumulation of genetic damage in the aging brain, with Alzheimer’sshowing the most severe form of this damage, called double strand breaks.Though the source of the damage is not yet clear, one culprit, he said, may bethe accumulation of metals in the brain over time, particularly iron.Neurons use more energy than most other cells, Yankner said.With the brain’s increase in complexity over time, its energy demands alsorose. Iron plays a key role in a cell’s energy-producing mitochondria, and soiron accumulation leading to genetic damage could be a byproduct of ourneuron-rich, energy-gobbling brains.“Aging is a balance between wear and tear and repair. Whereyou wind up in that balance determines how you do,” Yankner said.