Patterns of brain activity could predict early Alzheimer’s symptoms in mice

Written by Heather Jones, Assistant Editor

Researchers at Gladstone Institutes (CA, USA) have been investigating the cerebral activity associated with Alzheimer’s disease. In a new study published in Cell Reports, they demonstrate that particular patterns of brain activity could indicate whether a young mouse will develop Alzheimer’s prior to any noticeable signs of memory loss.

In previous research, senior author of the study Yadong Huang (Gladstone Institutes) and his team investigated sharp-wave ripples (SWRs), which are brain patterns that play a direct role in spatial learning and memory formation. They occur when the brain of a mouse or human replays a recent memory of moving through a space.

Previous research using mice carrying ApoE4revealed that these mice often developed signs of memory loss with age.

“SWRs have two important measurable components: abundance and short gamma (SG) power,” commented Emily Jones (Gladstone Institutes), lead author of the new study. “Broadly, SWR abundance predicts how quickly an ApoE4 mouse can learn and memorize how to get through a maze, and SG power predicts how accurate that memory will be.”

The earlier study revealed that aging ApoE4 mice have lower SWR abundance and weaker SG power than healthy aging mice. This led Jones to hypothesize that by measuring SWR activity in mice they could predict memory problems in aging ApoE4 mice.

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Researchers tested SWR and spatial memory on ApoE4 mice with a 1-month interval. The results confirmed the hypothesis, demonstrating that mice with fewer SWRs and lower SG are likely to have worse spatial memory.

Curious to discover how the relationship between brain patterns and memory applied over a lifetime, the team went on to measure SWRs in ApoE4 mice from an early age, through into old age.

The results revealed that deficits in SWR abundance and SG power at an early age could predict performance in memory tests 10 months later, the equivalent of 30 years for a human.

The findings suggest that these cerebral tests could potentially be carried out on humans to predict Alzheimer’s disease long before any noticeable signs of memory loss appear.

Following on from this discovery, Huang and his team plan to determine whether SWRs in Alzheimer’s patients exhibit properties similar to those seen in the mouse models, which would in turn indicate that SWRs are indeed predictive of Alzheimer’s in humans.

This would have significant scientific and clinical implications. First, SWRs could be used to select participants for clinical trials testing drugs designed to prevent or delay onset of Alzheimer’s. Second, these tests could be used to test the effects of drugs over time.

Huang added: “I feel strongly that Alzheimer’s research should not just focus on pathology, but use functional alterations like SWR deficits to guide research and drug development. Our new findings support this kind of approach.”

Sources: Jones EA, Gillespie AK, Yoon SY, Frank LM, Huang Y. Early hippocampal sharp-wave ripple deficits predict later learning and memory impairments in an Alzheimer’s disease mouse model. Cell Rep. doi:10.1016/j.celrep.2019.10.056 (2019);