The Overactive Brain
Michela Gallagher was studying aging in lab rats when an unusual finding launched her on a translational journey that now sees her poised to initiate a Phase III trial of a drug to delay the onset of Alzheimer’s dementia.
Michela Gallagher |
In some ways, I’ve always been a neuroscientist – I was always very interested in memory and I became fascinated by the frequency and commonality of memory loss as people age. Today, my work lies at the intersection of normal age-related changes in memory, the pre-dementia state known as amnesic mild cognitive impairment (aMCI) and the full-blown symptoms that we recognize as dementia. Alzheimer’s doesn’t develop overnight – it’s an exceedingly slow progression from normal aging to dementia. The transitional phase of aMCI in which memory impairment is somewhat greater than expected for a person’s age can last a decade before progression to the point of a clinical diagnosis of early Alzheimer’s dementia.
I didn’t set out to study Alzheimer’s disease. My work in this field hinges on a surprising finding from our studies on memory loss in aging rodents. In rats with memory loss, a subset of neurons critical for memory in the hippocampus are overactive. Other researchers made the same observation in patients with aMCI. This happens to some extent in normal aging but when Alzheimer’s pathology begins to emerge, hippocampal hyperactivity is driven higher and higher. Initially, it was thought that this might be a compensatory mechanism – the neurons working harder to try to hang onto making memories and overcoming damage. But our work in rats told us that this wasn’t true. To find out what the functional significance was, we had found ways to bring the activity down to normal levels. The result was to improve the memory deficits usually seen in those animals, suggesting that overactivity was causing rather than compensating for damage.
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