Tau conformational changes in aging‐related tau astrogliopathy.

Abstract

AbstractBackgroundThe presence of aging‐related tau astrogliopathy (ARTAG) is highly frequent, but poorly characterized in aging brain and neurodegeneration. Over the abnormal tau accumulation processes, tau protein undergoes pathological modifications and the sequency of these pathological events can be associated with different levels of tau aggregation.MethodTo evaluate the frequency of ARTAG in a large population‐based study, we analyzed brain sections immunostained with phosphor tau (AT8) of 1151 individuals with previous neuropathological evaluation. Further, to investigate early stages of tau protein aggregation in ARTAG, we performed additional immunohistochemistry in the amygdala of 32 cases with ARTAG pathology using the following tau antibodies: AT100 and Tau‐C3.ResultARTAG was frequently observed in cognitively normal individuals independent of concomitant neurodegenerative disease. Higher burden of Alzheimer‐type pathology was observed in ARTAG compared to non‐ARTAG. Also, presence of more than one pathology (mixed pathology) was higher in ARTAG compared to non‐ARTAG (p<0.001). Additionally, AT100 immunoreactive ARTAG was found in overall cases, while Tau‐C3 immunoreactive ARTAG was not observed in 12 cases (36%), showing different mature stage for ARTAG compared to neurofibrillary tangles.ConclusionDifferent immunological markers can be found in ARTAG and Alzheimer’s neurofibrillary pathology in early stages of tau pathological processing, suggesting different levels of abnormal tau aggregates among cases with ARTAG pathology.