Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Abstract Background In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is transentorhinal region, a subregion within medial temporal lobe largely overlaps with area 35, and entorhinal cortex. Here we used tau‐PET imaging to investigate sequence of tau pathology progression human across regions in posterior‐medial system. Our objective was study how related functional connectivity, regional atrophy, memory performance. Method We included 215 β‐amyloid negative cognitively unimpaired, 81 positive unimpaired 87 individuals mild cognitive impairment, who each underwent [18]F‐RO948 [18]F‐flutemetamol amyloid PET imaging, structural T1‐MRI assessments as part Swedish BioFINDER‐2 study. Result First, event‐based modelling revealed cortex 35 show earliest signs accumulation followed by anterior posterior hippocampus, 36 parahippocampal later stages, became abnormal neocortical finally parietal brain (see Figure 1). Second, individuals, increased load local atrophy cortex, hippocampus several subregions associated distant hippocampus. Tau load, but not these lower Further, tau‐related reductions connectivity critical networks between system were this early impairment. Finally, patients association performance partially mediated hippocampal atrophy. Conclusion summary, our findings highlight its disease‐stage specific While might affect via reduced lobe‐cortical networks, impairment impaired