• Shorena Janelidze, Niklas Mattsson, Sebastian Palmqvist, Ruben Smith, Thomas G Beach, Geidy E Serrano, Xiyun Chai, Nicholas K Proctor, Udo Eichenlaub, Henrik Zetterberg, Kaj Blennow, Eric M Reiman, Erik Stomrud, Jeffrey L Dage, and Oskar Hansson.
• Clinical Memory Research Unit, Lund University, Lund, Sweden. shorena.janelidze@med.lu.se.
• Nat. Med. 2020 Mar 1; 26 (3): 379-386.

AbstractPlasma phosphorylated tau181 (P-tau181) might be increased in Alzheimer's disease (AD), but its usefulness for differential diagnosis and prognosis is unclear. We studied plasma P-tau181 in three cohorts, with a total of 589 individuals, including cognitively unimpaired participants and patients with mild cognitive impairment (MCI), AD dementia and non-AD neurodegenerative diseases. Plasma P-tau181 was increased in preclinical AD and further increased at the MCI and dementia stages. It correlated with CSF P-tau181 and predicted positive Tau positron emission tomography (PET) scans (area under the curve (AUC) = 0.87-0.91 for different brain regions). Plasma P-tau181 differentiated AD dementia from non-AD neurodegenerative diseases with an accuracy similar to that of Tau PET and CSF P-tau181 (AUC = 0.94-0.98), and detected AD neuropathology in an autopsy-confirmed cohort. High plasma P-tau181 was associated with subsequent development of AD dementia in cognitively unimpaired and MCI subjects. In conclusion, plasma P-tau181 is a noninvasive diagnostic and prognostic biomarker of AD, which may be useful in clinical practice and trials.

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