“It’s become increasingly clear that Alzheimer’s Disease is a complex disorder,” states Andrew Saykin, PsyD, Raymond C. Beeler Professor of Radiology and Imaging Sciences and Director of the Indiana Alzheimer Disease Center (IADC) and Indiana University Center for Neuroimaging (CfN). “We need to take a multi-dimensional approach.”
The faculty of the centers are taking innovative approaches to examine exciting new avenues for research and discovering new facets of the disease. “Beta-amyloid and Tau [proteins] are important, but they’re not enough to explain the disease.” The researchers at these centers are pioneering work in Alzheimer’s Disease and its relationship to and impact on aspects such as inflammation, cerebrovascular disease, cancer, Type 2 diabetes, traumatic brain injury and many other health conditions. To this end, the center researchers perform an array of molecular, genetic and imaging-based analysis of patients, looking for biomarkers that may predict onset of the disease and present new therapeutic targets. They currently have 25 leading candidate genes that they are examining.
Alzheimer’s Disease (AD) research has grown leaps and bounds since it used to be only diagnosed post mortem. Now, researchers can examine real-time changes in the brain in AD patients. These quantitative phenotypes can be measured using a variety of imaging techniques, including positron emission tomography (PET) scans and multiple advanced magnetic resonance (MR) imaging techniques and modalities. The research group is also working on noninvasive measurements of brain architecture that gives a quantitative readout during memory tasks patients are asked to perform while in the scanner. The researchers are just beginning to scratch the surface of possibilities, pairing genetic and imaging data to better understand the disease and its progression.
“We have tremendous amounts of multimodal imaging and genetic data. Right now the great challenge is having the right informatics strategy,” states Saykin. “We’re connecting the dots.” Indiana University’s supercomputing facilities come into play in the strategic plan on how to integrate complex and rich data sets. The researchers are collaborating with other faculty investigators in Bloomington to generate better models of brain connectivity (the “connectome”) and relate these models to genetics.
The AD research community has shifted vision to early detection of the disease. “We need to use biomarkers to try to understand if they have underlying neurodegeneration or some other reason. For patients headed for Alzheimer’s Disease, we [could] do intervention.” Such advanced imaging technology is now available to detect changes in the brain in patients who perform normally on memory tasks but have “cognitive complaints” of general forgetfulness. The research group is looking to understand which individuals are at risk even before they exhibit task performance problems.
While imaging technology and research evolves to allow earlier detection of AD, it also means analysis of AD patients on an individual level. The center continues to produce data and make discoveries that fall in line with the IU Precision Health Initiative. “[Pharmaceutical treatment] is probably a cocktail, similar to HIV treatment. Maybe everyone doesn’t need the same cocktail – that’s precision medicine.”
PHOTO: Yu-Chien Wu & Sourajit Mustafi