The biomarker that detects signs of Alzheimer's disease (lat. Morbus Alzheimerianus, AD) was developed by scientists by the University of Zagreb. The worldwide increase of AD, a long-lasting morbid type of dementia, is currently one of the biggest global public health challenges. A wealth of evidence emerged during over more than 110 years of disease research suggest that the pathological changes associated with AD start decades before the onset of clinical symptoms. This long progression of neurodegeneration is irreversible by the stage of symptomatic disease, which may account for failure 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 AD in cognitively intact individuals, before the occurrence of the first symptoms (pre-clinical).
Magnetoencephalography (MEG), a direct, real-time and absolutely non-invasive measure of neuronal activity, is an underexplored tool in the search for biomarkers of AD. Scientists from the University of Zagreb used MEG measurements to localize auditory gating generators evoked by the simple oddball hearing test.
Sanja Josef Golubic Ph.D., physicists at the Faculty of Science, the University of Zagreb, found the binary biomarker of Alzheimer’s disease within the topography of the auditory sensory gating network. Her results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete detector of AD at the individual level: sustained mPFC activation to the both oddball tones in healthy elderly; absence of mPFC activation to the standard tone only in a possible preclinical stage and its absolute inactivation in symptomatic AD. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a research sample. The results demonstrate the high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages.
The new biomarker does not require estimation of cut-off levels or standardization processes, which is the main problem with previously proposed AD markers. It is absolutely non-invasive, it is not based on the use of group means and is not associated with statistically significant changes in a continuous variable. Its strength lies in the simplicity of a binary value—an activated or non-activated neural generator. The low sensitivity to individual heterogeneity and the variability due to its binary nature is probably the most important property of the proposed biomarker.
In conclusion, the localization of a discrete prefrontal auditory gating activation is a highly promising biomarker of Alzheimer's disease at the individual level with capacity of following the evolution of the pathophysiological process of disease. The large effect size, absolute non-invasiveness and statistical independence give this biomarker a high potential for prompt translation into clinical use. The next steps in developing the biomarker include testing with large independent samples and assessment in longitudinal clinical studies that would track non-symptomatic elderly with prefrontal gating impairment until the first clinical symptoms appear and finally to autopsy for confirmation of disease.