The presence of plasma phosphorylated tau181 (P-tau181) in patients may aid in the diagnosis of Alzheimer disease (AD), a study in Natural Medicine suggests. The findings from this study also indicate that the P-tau181 biomarker may aid in identifying prognostic outcomes of patients with AD.

The study featured 3 cohorts comprised of 589 participants with unimpaired cognition as well as patients with mild cognitive impairment (MCI), AD dementia, and non-AD neurodegenerative diseases. The prospective Swedish BioFINDER study contributed to the cohorts, whereas the third cohort was derived from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program at the Banner Sun Health Institute.

Cohorts 1 (n=182) and 2 (n=344) included participants who were either cognitively unimpaired with a high prevalence of Aβ positivity (>50%), patients who were Aβ+ with MCI, AD dementia, or patients with non-AD neurodegenerative disease. The third cohort included patients with AD dementia (n=16) and non-AD neuropathologically confirmed cases (n=47) who provided plasma samples 0.02 to 2.9 years prior to death.

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Relative to non-AD cases, plasma P-tau181 was elevated in patients with neuropathologically confirmed cases of AD (P <.001). Increased plasma P-tau181 accurately differentiated neuropathologically confirmed AD cases vs non-AD cases (area under the curve [AUC], 0.85). Increased P-tau181 was associated with significantly increased levels of Aβ PET in cohorts 1 (β = 0.54, P <.001) and 2 (β = 0.53, P <.001). Compared with the Aβ–cognitively unimpaired cases in cohort 1, there were significantly higher levels of P-tau181 in Aβ+ cognitively unimpaired (P =.044), Aβ+ MCI (P <.001), and Aβ+ AD dementia (P <.001). There was also higher P-tau181 in non-AD disease groups relative to Aβ–cognitively unimpaired cases (all P =.001).

Additionally, baseline plasma P-tau181 predicted progression to AD dementia, reflected by increased baseline plasma P-tau181 in participants who later developed AD dementia vs participants that did not develop any dementia (both Aβ+ and Aβ– individuals) or developed dementia related to other causes (F=45.7, P <.001; post hoc tests: P <.001). In an analysis adjusted for age, sex, and education, each 1 standard deviation increment in the log of baseline plasma P-tau181 correlated with an increased risk of future AD dementia (hazard ratio [HR], 3.8; P <.001). Abnormal levels of P-tau181 at >1.81pgml–1 also correlated with a greater risk of future AD dementia compared to normal plasma levels of P-tau181 at ≤1.81pgml–1 (HR, 10.9; 95% CI, 5.0–24.0; P <.001).

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The investigators suggest that “plasma P-tau181 can be used as a blood-based biomarker of cerebral PHF-tau pathology,” which may be used in “studies with longitudinally banked plasma samples to study the effects on tau pathology of risk factors, protective factors, and different interventions.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Janelidze S, Mattsson N, Palmqvist S, et al. Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia [published online March 2, 2020]. Nat Med. doi: 10.1038/s41591-020-0755-1.