Novel Brain Imaging May Detect Preclinical Alzheimer’s Disease Interview with:
Dr. Sanja Josef Golubic, dr. sc

Department of Physics, Faculty of Science
University of Zagreb, Croatia What is the background for this study?

Response: Our study was aimed to search the topological biomarker of Alzheimer’s disease. A recent evidences suggest that the decades long progression of brain degeneration that is irreversible by the stage of symptomatic Alzheimer’s disease, may account for failures to develop successful disease-modifying therapies. Currently, there is a pressing worldwide search for a marker of very early, possibly reversible, pathological changes related to Alzheimer’s disease in still cognitively intact individuals, that could provide a critical opportunity for evolving of efficient therapeutic interventions.

Three years ago we reported the discovery of the novel, fast brain pathway specialized for rapid processing of the simple tones. We named it gating loop. Gating loop directly links auditory brain areas to prefrontal brain area. We have also noticed the high sensitivity of the gating loop processing on AD pathology. It was inspiration to focus our Alzheimer’s disease biomarker search in the direction of prefrontal brain activation during listening of simple tones. What is your approach in the search for preclinical marker of Alzheimer’s disease?

Response: In our approach we used the novel brain imaging technique called magnetoencephalography. We recorded the ultra-weak magnetic fields that our brain normally produces during listening a series of repeating tone with novel tone randomly interpolated within the series. What are the main findings?

Response: Our main findings showed that the healthy individuals activated frontal brain area to both tones, repeating and novel. To the contrary, the symptomatic Alzheimer’s patients lack any frontal activity, regardless of a tone type. The sub-group of healthy elderly in the possible preclinical phase of disease, activated frontal brain area to the novel tone but lack activation on the repeating tone. This findings shows a high accuracy, sensitivity and specificity (100%) in identifying symptomatic AD patients within a research sample. What should readers take away from your report?

Response: The proposed biomarker of Alzheimer’s disease can detect the illness before the first clinical symptoms. Our biomarker has a discrete nature: detects individually activated or not activated a specific frontal brain area during the listening of simple tones. This means that it is not based on the significantly increased or decreased value of some measured variable in patient group vs healthy group. For that reason the proposed biomarker does not require estimation of uniform cut-off levels or standardization processes and has low sensitivity to individual heterogeneity and variability, the main problems of other biomarkers. In addition, our biomarker is absolutely non-invasive, we are only record ultra-weak magnetic fields that our brain normally produces during the tone listening. What recommendations do you have for future research as a result of this study? 

Response: Proposed biomarker is a promising AD marker at the individual level, however, this approach is the result of a basic research study. Translation into the clinical use requires testing in a large independent clinical sample and requires assessment in longitudinal studies. Ideally, studies would track non-symptomatic elderly with impaired frontal brain activation to the repeating tones until the first clinical symptoms appear and finally to autopsy for confirmation of disease. Is there anything else you would like to add?

Response: I would like to emphasize that a significant contribution to this discovery has also been made by Cheryl Aine, leader of USA projects, from Department of Radiology, University of New Mexico School of Medicine; Selma Supek, leader of Coatian project, from Department of Physics, Faculty of Science, University of Zagreb; Julia Stephen, Director of MEG/EEG Core at Mind Research Network; John Adair, Director of the Memory Disorders Clinic at the VA Medical Centre in Albuquerque and Janice Knoefel, from Department of Neurology, New Mexico School of Medicine.

Any disclosures?

This work was supported by NIH grants R01 AG029495 and R01 AG020302, by the Department of Energy grant DE-FG02-99ER62764 to the Mind Research Network, the Radiology Department at UNM SOM and, the Research Service at the New Mexico VA Health Care System, and by the Croatian Ministry of Science, Education and Sport (grant 199-1081870-1252). Thank you for your contribution to the community.


Josef Golubic, S., Aine, C. J., Stephen, J. M., Adair, J. C., Knoefel, J. E. and Supek, S. (2017), MEG biomarker of Alzheimer’s disease: Absence of a prefrontal generator during auditory sensory gating. Hum. Brain Mapp., 38: 5180–5194. doi: 10.1002/hbm.23724

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.


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