Cognitive brain circuits and the spread of tau in vivo in humans

Alzheimer disease (AD) is pathologically defined by selective neuronal loss and decrease in synaptic density, the accumulation of fibrillar β amyloid plaques and intra- and extraneuronal deposition of phosphorylated tau as neurofibrillary tangles, neuropil threads and dystrophic neurites [6]. Dementia has been recognized as a global health care problem associated with significant economic and social burden. It is therefore important to get a better understanding of how amyloid and tau aggregation relate to brain dysfunction and to cognitive symptoms in humans, as this is a prerequisite for rationally developing disease-modifying and cognitive enhancing therapies. The ability to image amyloid plaques in vivo has revolutionized AD research. Recently, different tau PET tracers have entered the clinical development phase. Compared to amyloid, tau aggregation likely has a more direct effect on the functioning of cognitive brain circuits which determines the cognitive performance of individuals and the clinical manifestations of the disease. Combined tau PET imaging and fMRI over the course of the disease will provide insight into how tau aggregation affects the function of cognitive brain circuits.