Age-Related Memory Loss vs. Alzheimer’s Disease
The winter issue of Columbia University’s Magazine has an article on Your Beautiful Brain: Dispatches from the Frontiers of Neuroscience. I was particularly interested in the account of Nobel Prize-winning Professor Eric Kandel‘s 50+ years of research that began by looking at Aplysia — a “blobby mollusk with protruding feelers that resemble rabbit ears” — thus contributing to the mollusk’s nickname, the “sea hare.”
Clearly to Professor Kandel, the mollusks’ brains were beautiful, not least because their comparatively large neural structures provided an accessible way to study more complex structures such as the human brain. Dr. Kandel, now 87, admits that “hunches” have played a role in his research.
From Columbia Magazine:
Today, as neuroscientists worldwide pursue remedies for Alzheimer’s and age-related memory loss, Kandel’s half century of findings are considered indispensable. Substantive therapies for Alzheimer’s in particular are “poised for success,” says Jessell, a colleague of Kandel’s for thirty-five years. “We’re on the cusp of making a difference.” But accompanying that claim is a caveat; the fledgling remedies are not panaceas. “We’re not necessarily talking about curing the disease,” he says. “But we are talking about slowing the symptomatic progression of the disease so significantly that lifestyles are improved in a dramatic way. If in ten years we have not made significant progress, if we are not slowing the progression of Alzheimer’s, then we have to look very seriously at ourselves and ask, ‘What went wrong?’”
Breakthroughs could happen sooner, however. Some of the Alzheimer’s medications available now “probably work,” says Kandel, except for one obstacle: “By the time patients see a physician, they’ve had the disease for ten years. They’ve lost so many nerve cells, there’s nothing you can do for them.” Possibly, with earlier detection, “those same drugs might be effective.” That’s not a certainty, insists Kandel, only a “hunch.”
Professor Kandel has also explored the biological differences between “ordinary” age-related memory loss and Alzheimer’s Disease.
Years ago, Kandel had another hunch — that age-related memory loss was not just early-stage Alzheimer’s, as many neuroscientists believed, but an altogether separate disease. After all, not everyone gets Alzheimer’s, but “practically everyone,” says Kandel, loses some aspects of memory as they get older. And MRI images of patients with age-related memory loss, as demonstrated by CUMC neurology professor Scott Small ’92PS, have revealed defects in a brain region different from those of the early-stage Alzheimer’s patients.
Kandel also knew mice didn’t get Alzheimer’s. He wondered if they got age-related memory loss. If they did, that would be another sign the disorders were different. His lab soon demonstrated that mice, which typically have a two-year lifespan, do exhibit a significant decrease in memory at twelve months. With that revelation, Kandel and others deduced Alzheimer’s and age-related memory loss are distinct, unconnected diseases.
Then Kandel’s lab (again, with assistance from Small) discovered that RbAp48 — a protein abundant in mice and men — was a central chemical cog in regulating memory loss. A deficit of RbAp48 apparently accelerates the decline. Knocking out RbAp48, even in a young mouse brain, produces age-related memory loss. But restoring RbAp48 to an old mouse brain reverses it.
Now what may be the eureka moment — this from Gerard Karsenty, chairman of CUMC’s department of genetics and development: bones release a hormone called osteocalcin. And Kandel later found that osteocalcin, upon release, increases the level of RbAp48.
“So give osteocalcin to an old mouse, and boom! Age-related memory loss goes away.”
The same may prove true in humans. A pill or injectable could work, says Kandel: “Osteocalcin in a form people can take is something very doable and not very far away.” In less than a decade, age-related memory loss might be treatable. “This,” he says, “is the hope.”
For more on beautiful brains, read the full article on Columbia University’s website.