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Military veterans who experience blast-related traumatic brain injuries often suffer from chronic cognitive and neurobehavioral syndromes. Reports of abnormal tau processing following blast injury have raised concerns that some cases may have a neurodegenerative basis. Rats exposed to repetitive low-level blast exhibit chronic neurobehavioral traits and accumulate tau phosphorylated at threonine 181 (Thr181). Using data previously reported in separate studies we tested the hypothesis that region-specific patterns of Thr181 phosphorylation correlate with behavioral measures also previously determined and reported in the same animals. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization. There were no correlations with levels in amygdala or posterior neocortical regions. Particularly striking were asymmetrical effects on the right and left hippocampus. No systematic variation in head orientation toward the blast wave seems to explain the laterality. Levels did not correlate with behavioral measures of hyperarousal. Results were specific to Thr181 in that no correlations were observed for three other phospho-acceptor sites (threonine 231, serine 396, and serine 404). No consistent correlations were linked with total tau. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and the hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself. They also suggest an association linking blast injury with tauopathy, which has implications for understanding the relationship of chronic blast-related neurobehavioral syndromes in humans to neurodegenerative diseases.

Epidemiological projections of the prevalence of Alzheimer's disease (AD) and related dementias, the rapidly expanding population over the age of 65, and the enormous societal consequence on health, economics, and community foretell of a looming global public health crisis. Currently available treatments for AD are symptomatic, with modest effect sizes and limited impact on longer term disease outcomes. There have been no newly approved pharmaceutical treatments in the last decade, despite enormous efforts to develop disease-modifying treatments directed at Alzheimer's-associated pathology. An unprecedented collaborative effort of government, regulators, industry, academia, and the community at-large is needed to address this crisis and to develop an actionable plan for rapid progress toward successfully developing effective treatments. Here, we map out a course of action in four key priority areas, including (1) addressing the fundamental mechanisms of disease, with the goal of developing a core set of research tools, a framework for data sharing, and creation of accessible validated and replicated disease models; (2) developing translational research that emphasizes rapid progress in disease model development and better translation from preclinical to clinical stages, deploying leading technologies to more accurately develop predictive models; (3) preventing AD through the development of robust methods and resources to advance trials and creating fundamental resources such as continuous adaptive trials, registries, data repositories, and instrument development; and (4) innovating public/private partnerships and global collaborations, with mechanisms to incentivize collaborations and investments, develop larger precompetitive spaces, and more rapid data sharing.