CSF tau phosphorylation at sites 217 and 205 mediate the relationship between PET amyloid and downstream AD markers

Associations between amyloid and downstream measures of Alzheimer disease (AD) are often lacking. In autosomal dominant AD (ADAD), cerebrospinal fluid (CSF) phosphorylated tau 217 and 181 (pT217 and pT181) increase shortly after amyloid positron emission tomography (PET), followed by tau 205 (pT205), then tau PET. Each site also tracks closely with disease progression and is associated with longitudinal cognitive decline. Collectively these findings lead to the question of which p‐tau sites affect the relationship between amyloid and downstream AD markers (i.e., tau, MRI cortical thickness, Clinical Dementia Rating [CDR] Scale status), and more specifically whether they mediate such associations.