APOE differentially moderates cerebrospinal fluid and plasma phosphorylated tau181 associations with multi-domain cognition

Biofluid markers of phosphorylated tau181 (p-tau181) are increasingly popular for the detection of early Alzheimer's pathologic changes. However, the differential dynamics of cerebrospinal fluid (CSF) and plasma p-tau181 remain under investigation. We studied 727 participants from the Alzheimer's Disease Neuroimaging Initiative with plasma and CSF p-tau181 data, apolipoprotein (APOE) 84 carrier status, amy-loid positron emission tomography (PET) imaging, and neuropsychological data. Higher levels of plasma and CSF p-tau181 were observed among APOE 84 carriers. CSF and plasma p-tau181 were significantly associated with memory, and this effect was greater in APOE 84 carriers. However, whereas CSF p-tau181 was not significantly associated with language or attention/executive function among 84 carriers or non -carriers, APOE 84 status moderated the association of plasma p-tau181 with both language and atten-tion/executive function. These findings lend support to the notion that p-tau181 biofluid markers are useful in measuring AD pathologic changes but also suggest that CSF and plasma p-tau181 have unique properties and dynamics that should be considered when using these markers in research and clinical practice. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )