The Adult Neurogenesis Theory of Alzheimer’s Disease Predicts Where Tauopathy Develops in the Brain

Adult neurogenesis is impaired in Alzheimer’s disease (AD) and contributes to neuronal and cognitive dysfunction. Furthermore, efficient neurogenesis promotes cognitive resilience. I recently proposed a theory suggesting that neurogenesis plays a more central role in the pathogenesis of AD. The main hypothesis posits that new neurons harboring tau seeds propagate tauopathy as they mature and integrate into the brain. The aim of this study is to demonstrate that the theory successfully predicts the distribution of the earliest foci of tauopathy in AD. To this end, I synthesized data from the literature regarding the earliest localizations of tauopathy in AD. I then indicated where one would expect to find the earliest seeds of tauopathy if the theory were true. Finally, I compared the localization data with the theory’s predictions. Overall, the theory’s predictions were entirely consistent with the initial localization of tauopathy. Specifically, the theory is consistent with the exclusively neuronal and somatodendritic involvement of tauopathy; the preference for layer II and the transentorhinal/entorhinal complex; the early involvement of subcortical nuclei; phenotypic heterogeneity; differences between early- and late-onset AD; hemispheric asymmetries; and clinical-anatomical convergence. The theory demonstrates predictive power, economicity, compatibility with other theories, and generalizability to other diseases.