Through the new NIH-funded Alzheimer’s Disease Precision Models Center at Indiana University School of Medicine and The Jackson Laboratory, researchers are developing mouse models that more closely mimic human Alzheimer’s disease.
But their work doesn’t stop at creating the model; the team is also building a preclinical testing pipeline through which new drug therapies can be tested.
This one-two punch will greatly accelerate the process by which therapies are successfully moved forward to human Alzheimer’s disease clinical trials.
Could some types of Alzheimer’s disease be slowed or even stopped through healthy lifestyle changes such as exercise and diet — even if we are aging and genetically susceptible to the disease?
In his lab, Gareth Howell, Ph.D. and his team have uncovered evidence that poor lifestyle choices (think junk foods, saturated fats, minimal fruits and vegetables) may have a powerful impact in making us more prone to Alzheimer’s. But (and here’s the good news), healthy choices may potentially reduce the risk of the disease.
At JAX’s new Alzheimer's Disease Precision Models Center, Howell is genetically manipulating mice to understand how unhealthy lifestyle habits trigger immune responses in the brain, leading to a cascade of events that may ultimately impair thinking and memory, as in Alzheimer’s disease.
If Howell’s findings hold true for humans, then lifestyle changes could be a major way to lessen the impact of Alzheimer’s disease, saving millions of people from the devastating losses of thinking and memory.
Alzheimer’s is complex and involves many different genetic deviations and different genes all interacting and conspiring to lead to disease.
Computational biologist Gregory Carter, Ph.D. and his team have set out to identify which genetic variants are most likely to trigger Alzheimer’s disease, using… math.
From trillions and trillions of data points generated by analyzing human genomes at the most basic levels, Carter is using a new, powerful mathematical approach to identify biomarkers of Alzheimer’s disease, before symptoms emerge.
Ultimately, Carter's lab will develop new computational tools in freely available software for a broad range of genetic applications, giving researchers around the world the abilities to detect and interpret genetic interaction effects and provide more precise models of the genetic influence on the risk for Alzheimer’s. From there, targeted treatments can be tested.
Why is it that many people’s brains have been found to have the signature defects of Alzheimer’s disease — neurofibrillary tangles and beta amyloid plaques — yet they never showed the thinking and memory problems of the disease while they were alive?
Some people, it seems, are protected from Alzheimer’s disease and some aren’t.
Using mouse models, JAX neuroscientist Catherine Kaczorowski, Ph.D. aims to identify the “biomarkers of resilience” — the genes and molecules that determine how rapidly someone’s thinking declines (or doesn’t!). Her results will be especially powerful when combined with simultaneous drug development and, ultimately, clinical trials with humans affected by Alzheimer’s.
If Kaczorowski is successful in uncovering the genes that protect some people from the symptoms of Alzheimer’s, we may see drug treatments that mimic those genes, with the goal of protecting us all from Alzheimer’s.