Development and Performance Assessment of a Novel Plasma p-Tau181 Assay Reflecting Tau Tangle Pathology in Alzheimer's Disease
Tagai, K.; Tatebe, H.; Matsuura, S.; Hong, Z.; Kokubo, N.; Matsuoka, K.; Endo, H.; Oyama, A.; Hirata, K.; Shinotoh, H.; Kataoka, Y.; Matsumoto, H.; Oya, M.; Kurose, S.; Takahata, K.; Ichihashi, M.; Kubota, M.; Seki, C.; Shimada, H.; Takado, Y.; Kawamura, K.; Zhang, M.-R.; Soeda, Y.; Takashima, A.; Higuchi, M.; Tokuda, T.
Show abstract
Several blood-based assays for phosphorylated tau (p-tau) have been developed to detect brain tau pathologies in Alzheimers disease (AD). However, plasma p-tau measured by currently available assays is influenced by brain amyloid and, therefore, could not accurately reflect brain tau deposits. Here, we devised a novel immunoassay that can quantify N- and C-terminally truncated p-tau fragments (mid-p-tau181) in human plasma. We measured plasma p-tau181 levels in 164 participants who underwent both amyloid and tau positron emission tomography (PET) scans using mid-p-tau181 and conventional p-tau181 assays. The mid-p-tau181 assay displayed stronger correlations with tau PET accumulation than the conventional assay in the AD continuum and accurately distinguished between tau PET-positive and -negative cases. Furthermore, the mid-p-tau181 assay demonstrated a trajectory similar to tau PET alongside cognitive decline. Consequently, our mid-p-tau181 assay could be useful in evaluating the extent of brain tau burden in AD.
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