New way to predict Alzheimer’s disease-like memory loss before it strikes

For a person with Alzheimer’s disease, there’s no turning back the clock.

By the time she begins to experience memory loss and other worrisome signs, cognitive decline has already set in.

And decades of clinical trials have failed to produce treatments that could help her regain her memory.

In a new study, researchers are approaching this devastating disease from a different angle.

They demonstrate that particular patterns of brain activity can predict far in advance whether Alzheimer’s-like memory deficits will appear in old age.

The research was conducted by a team at Gladstone Institutes.

In the previous study, the team examined a type of brain activity called sharp-wave ripples (SWRs), which play a direct role in spatial learning and memory formation in mammals.

SWRs occur when the brain of a resting mouse or human rapidly and repeatedly replays a recent memory of moving through space, such as a maze of a house.

The earlier study revealed that aging ApoE4 mice have lower SWR abundance than seen in healthy aging mice.

Carrying the ApoE4 gene is associated with an increased risk—but not a guarantee—of Alzheimer’s disease in humans.

Based on those results, the team hypothesized that measuring SWR activity could predict the severity of demonstrable memory problems in ApoE4 mice during aging.

In the study, the team recorded SWR activity in aging ApoE4 mice at rest. One month later, they had the mice perform spatial tasks to test their memory.

They found that mice with fewer SWRs were indeed more likely to have worse spatial memory deficits.

They also found that deficits in SWR abundance at an early age-predicted which mice performed worse on memory tasks 10 months later—the equivalent of 30 years for a human.

Since SWRs are also found in humans, these findings suggest that SWR abundance could potentially serve as early predictors of Alzheimer’s disease, long before memory problems arise.

The team plans to determine whether SWRs in Alzheimer’s patients show deficits in abundance similar to those seen in mouse models of the disease.

The lead author of the study is Gladstone Senior Investigator Yadong Huang.

The study is published in Cell Reports.

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