Résumé
Background Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (A beta) positivity as determined by position emission tomography (PET), and if an ordinal sequence of p-tau epitopes occurs at this incipient phase
Methods We measured CSF concentrations of p-taui8I, p-tau217 and p-tauzp in 171 participants across the AD continuum who had undergone A beta (F-18]AZD4.694.) and tau ([F-18]MK6240) position emission tomography (PET) and clinical assessment
Findings All CSF p-tau biomarkers were accurate predictors of cognitive impairment but CSF p-tau2i7 demonstrated the largest fold-changes in AD patients in comparison to non-AD dementias and cognitively unimpaired individuals. CSF p-tauzp and p-tau2i7 predicted A beta and tau to a similar degree but p-tauzp attained abnormal levels first. P-tauzp was sensitive to the earliest changes of A beta in the medial orbitofrontal, precuneus and posterior cingulate before global AP PET positivity was reached
Interpretation We demonstrate that CSF p-tauzp increases early in development of AD pathology and is a principal candidate for detecting incipient AP pathology for therapeutic trial application Copyright (C) 2022 Published by Elsevier B.V.