ALISO VIEJO, Calif.--(BUSINESS WIRE)--Brain insulin resistance is an abnormality in Alzheimer’s disease that contributes to neural cell damage and can be detected by a new blood test, according to a multi-site study that was published October 23 in the online issue of The FASEB Journal, The Journal of the Federation of American Societies for Experimental Biology. The highly statistically significant findings were made possible by a novel technique the researchers 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 Alzheimer’s disease (AD). This new blood test can accurately reflect development of AD up to 10 years prior to clinical onset, the study said.
Prior to this study, 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 (CNS) and other bodily 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.
The innovative approach used in this study allowed the researchers to extract and measure phosphorylated forms of IRS from isolated neural exosomes. Exosomes are tiny membrane-encased vesicles that are excreted from cells and are present in biological fluids such as blood, cerebrospinal fluid, etc. The ability to quantify the phosphorylated forms of IRS makes it possible to evaluate insulin resistance in the central nervous system using a blood-based assay with living patients.
The lead author of the study is Dimitrios Kapogiannis, M.D., Clinical Investigator for the National Institutes of Health, in Bethesda, Md. and the Intramural Research Program, National Institute on Aging, in Baltimore, Md.
The study found that for patients with AD and type 2 diabetes, the mean levels of the two extracted phosphorylated forms of IRS and their ratio (known as the insulin resistance index) were significantly different than the values for the healthy control group. In addition, the researchers reported that the mean level of the brain insulin resistance index for AD was significantly higher than for either type 2 diabetes or frontotemporal dementia (FTD). 100% of the patients with AD in the study were correctly classified with the researcher’s technique, as were 97.5% of patients with type 2 diabetes. Thus, AD patients can be distinguished from the control subjects by the level of brain insulin resistance as measured by the novel blood test.
“This study shows that insulin resistance is a major central nervous system metabolic abnormality in AD that contributes to neural cell damage,” said Dr. Ed Goetzl, the senior author on the study and the 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 multi-agent program for AD.”
The exosome-based technology used in the study will be further developed by NanoSomiX, a sponsor of the study, to produce a commercially available blood-based assay for researchers in academia and pharmaceutical companies. The assay will provide valuable information to those that are developing drugs for AD by using a routine and cost effective approach for early identification of subjects for inclusion in clinical trials.
"This new assay measuring brain insulin resistance further strengthens our portfolio of blood-based biomarker assays for AD using neuron-derived exosomes," said John Osth, President and CEO of NanoSomiX. “We believe our assays will prove instrumental in identifying early-stage AD patients for entry in clinical trials and thereby help to enrich the study population. We invite pharmaceutical companies and university researchers to contact us about collaborating or partnering to generate additional data."
NanoSomiX will also 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, in November.
Study sites for the just-published research included:
* Laboratory of Neurosciences, National Institute on Aging (Baltimore, Md.)
* The Department of Neurology, University of California-San Francisco (San Francisco, Calif.)
* Sanders-Brown Center on Aging, University of Kentucky (Lexington, Ky.)
* The Department of Neurology, Mayo Clinic (Rochester, Minn.)
* The Jewish Home of San Francisco (San Francisco, CA)
Resources
Alzforum: Exosomes Stand Out as Potential Blood Biomarkers
NIH Blog: NIH-supported study shows promise for blood test for Alzheimer’s disease
About NanoSomiX
NanoSomiX, Inc. 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 Alzheimer’s disease (AD). 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. The company is headquartered in Aliso Viejo, Calif. For more information, see www.nanosomix.com.