CSF tau phosphorylation at sites 217 and 181 are associated with preclinical and biphasic alterations in resting‐state functional connectivity in Autosomal Dominant AD

In autosomal dominant AD (ADAD), elevated cerebrospinal fluid (CSF) soluble phosphorylated tau (pT181) increases shortly after amyloid positron emission tomography. Recent advancements have identified additional phosphorylated tau sites, such as phosphorylated tau 217 and 205 (pT217 and pT205), which are associated with amyloid deposition and neuronal dysfunction, respectively. Degradation of cortical brain network resting‐state functional connectivity (RS‐FC) is typically observed at the onset of cognitive impairment and is most prevalent in regions where amyloid and tau accumulate. However, it is unknown how specific phosphorylated tau sites are associated with alterations in brain networks and contribute to the transition from asymptomatic to symptomatic AD.