Alzheimer’s Disease vs Age Related Memory Loss
There was a recent article discussing Nobel Prize-winning Professor Eric Kandel’s 50+ years of research on the topic of memory loss and Alzheimer’s Disease. It described how, while some of the newer medications are making a difference, they are often less effective because they are not used until well after the onset of the disease. Professor Kandel noted that with earlier detection the ability to help the victims of the disease could be significantly higher. He suggested that these medications really did little to cure the disease, but, caught early enough, they can slow the symptomatic progression of the disease so significantly that lifestyles are improved in a dramatic way.
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 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. Kandel’s lab 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.”