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Topographical overlapping of the AÎ² and Tau pathologies in the Default mode networks predicts Alzheimer's Disease with higher specificity

While Amyloid-plaques and Tau-tangles are the well-recognized pathologies of Alzheimers disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD. Using the recent advancements in the imaging technology, our newly developed quantification methods, and publicly available neuroimaging data from 303 individuals, we hypothesize and provide preliminary evidence that topographically overlapping Ab and Tau within the DMN play more critical roles in the underlying pathophysiology of AD than the Tau and/or Ab pathologies. We first showed that the probability of observing overlapping Ab and Tau is significantly higher within the DMN than outside DMN. Then we showed evidence that using Ab and Tau overlap can increase the reliability of the prediction of healthy individuals converting to MCI and a lesser degree converting from MCI to AD. These findings shed some light on the complex pathophysiology of AD and suggest that overlapping Ab and Tau pathologies within DMN might be a more reliable biomarker of AD for early detection and later diagnosis of the disease.