It’s the Myelin, not Michelin

            LOS ANGELES - Wisdom comes with age (doesn’t it?), but not without a brain process called myelination. Myelin is the fatty sheath coats of axons of the nerves, allowing efficient conduction of nerve impulses. It’s key to fast processing that underlies our higher cognitive functioning, including wisdom.

            Myelination sheaths axons until we reach about 50, but in later stages myelin becomes increasingly susceptible to damage. In Alzheimer’s &

Dementia, Dr. George Bartzokis, UCLA professor of neurology, suggests it’s late-stage myelin breakdown that promotes toxic amyloid-beta fibrils buildup that end in the brain and become plaques long tied to Alzheimer’s disease. These amyloid products then destroy more myelin, says Dr. Bartzokis, and disrupt brain signaling, leading to cell death and classic clinical Alzheimer’s signs. If correct, the research suggests a broader approach to therapeutic interventions for the disease.

            In a twist for modern science, Dr. Bartzokis tested his myelin model of Alzheimer’s by comparing modern imaging results with maps of cortical myelination published in the journal The Lancet - in 1901.

“Myelination is the single most unique aspect in which the human brain

differs from those of other species,” said Dr. Bartzokis, who directs the UCLA Memory Disorders and Alzheimer’s Disease Clinic. Myelin is made by specialized glial cells that become more vulnerable with age. “Myelination of the brain follows an inverted U-shaped trajectory, growing strongly until middle age. Then, it begins to breakdown,” he said. “Before the advent of modern medicine, very few persons lived beyond 50 and, as a species, we evolved to continue myelinating over our entire natural life span.”

            As a result, the volume of myelinated white matter increases to a peak at about 50, then slowly begins to reverse and decline in volume as we age. Myelin deposited in adulthood ensheaths increasing numbers of axons with smaller axon diameters, and spreads thinner and thinner, he said. It becomes more susceptible to ravages of age via environmental and genetic insults and slowly begins to break down.

            “The myelin breakdown process mimics the developmental process of

myelination, but this time in reverse,” Dr. Bartzokis said. “That’s what we think underlies the progressive spread of the neuritic plaques from late-myelinating regions toward the earlier-myelinating regions.” He noted a similar progression has been described clinically of the cognitive, functional and neurologic declines that accompany Alzheimer’s disease.

            In the study, he suggests myelin breakdown in late-myelinating regions releases iron and promotes development of the toxic amyloid oligomers and plaques, which destroy more myelin. Dr. Bartzokis said, “What’s important is these results have implications for novel therapeutic interventions that could target oligodendrocytes, myelin, and iron deposits in the brain.”

            The study was funded by the National Institute of Mental Health, National Institute on Aging, and the Psychiatry Services of the Dept. of Veterans Affairs. Po Lu, an assistant clinical professor in UCLA’s Dept. of Neurology, and Jim Mintz, professor of psychiatry at the David Geffen School of Medicine, were co-authors.