A new blood test that detects brain insulin resistance, as an abnormality associated with Alzheimer’s disease, was featured by meeting organizers as a “hot topic” presentation at the recent annual meeting of the Society for Neuroscience (SFN). Held in Washington, DC, November 15–19, the conference is the world’s largest meeting on brain science.
The presentation outlined new findings about how brain insulin resistance contributes to neural cell damage and is detectable with a new blood test. That assay is expected to provide valuable information to those who are developing drugs for Alzheimer’s disease (AD), by using a routine and cost-effective approach for early identification of subjects for inclusion in clinical trials.
Dimitrios Kapogiannis, MD
The study findings were presented at the SFN conference by Dimitrios Kapogiannis, MD, clinical investigator for the National Institutes of Health, Bethesda, Md, and for the intramural research program of the National Institute on Aging, Baltimore, Md. The findings were also recently published in the online issue of the Journal of the Federation of American Societies for Experimental Biology.1
The blood test will be further developed by NanoSomiX Inc, Aliso Viejo, Calif, a sponsor of the research, to produce a commercially available blood-based assay for researchers in academia and pharmaceutical companies.
NanoSomiX is dedicated to providing insight to researchers, clinicians, patients, their families and caregivers through the detection and management of neurodegenerative disorders via routine blood tests. The company’s flagship product is the first blood assay developed for the measurement of p-tau, a biomarker that studies have shown is tightly correlated with AD.
The research findings presented at the SFN conference were made possible by a novel technique developed for measuring brain insulin resistance in living patients. The technique involves using neuron-derived exosomes in the blood to measure insulin resistance in the brain as an indication of early-onset AD. This new test can accurately reflect development of AD up to 10 years prior to clinical onset, the study said.
Previously, it had not been possible to determine the prevalence of brain insulin resistance in living patients with AD. Nor had it been possible to determine how much time normally passes between the onset of brain insulin resistance and the appearance of clinically evident signs of AD.
In healthy individuals, the central nervous system and other body tissues respond to insulin with enhanced uptake of glucose, an energy source for cells. The term “insulin resistance” describes a diverse range of reduced responses to insulin in the brain and peripheral tissues. Insulin resistance causes diminished glucose uptake in similar regions of the brain in both AD and type 2 diabetes.
Brain insulin resistance is caused by low insulin receptor signaling. This deficiency is attributable to its association with abnormal amounts of two different forms of insulin receptor substrate (IRS). The extent of these abnormalities appears to increase in patients as they progress along the AD spectrum, from mild cognitive impairment (MCI) to probable AD, and with further worsening of AD.
“This study shows that insulin resistance is a major central nervous system metabolic abnormality in AD that contributes to neural cell damage,” says Ed Goetzl, MD, the senior author on the published study and originator of the exosome isolation technique. “As insulin resistance is a known condition in type 2 diabetes mellitus and is treatable with several classes of existing drugs, these treatments may be useful as part of a multiagent program for AD.”
Later this year, NanoSomiX will be introducing an exosome-based blood test for p-tau, a biomarker for AD that is currently detected only in cerebrospinal fluid and with PET scans. NanoSomiX is also developing additional blood-based assays for the management of AD as well as targeting other disease states. All testing is performed in a CLIA-approved laboratory in Irvine, Calif. For more information, visit NanoSomiX.
Reference
1. Kapogiannis D, Boxer A, Schwartz JB, et al. Dysfunctionally phosphorylated type 1 insulin receptor substrate in neural-derived blood exosomes of preclinical Alzheimer’s disease. Journal of the Federation of American Societies for Experimental Biology. Published online ahead of print October 23, 2014; doi: 10.1096/fj.14-262048.
