Plasma Tau Levels Serve as Biomarkers of Cognitive Decline in Lewy Body Dementia

Investigators measured p-tau181 and p-tau231 levels with in-house single molecule array assays and cognition with the Mini-Mental State Examination.

Findings from a recent study suggest that plasma phospho-tau 181 (p-tau181) and phospho-tau 231 (p-tau231) levels might be cost-effective and accessible biomarkers to assess cognitive decline in patients with Lewy body dementia (LBD).

Participants were included from the European-Dementia Lewy Body Consortium cohort, which enrolled a total of 10 centers that had harmonized diagnostic procedures between January 1, 2002, and December 31, 2020, and up to 5 years of follow-up. The final cohort for the current longitudinal study included 987 patients clinically diagnosed with probable LBD (n = 371), Parkinson disease (PD; n = 204), Alzheimer disease (AD; n = 207), and healthy controls (n = 205). 

Investigators, including corresponding author Maria C. Gonzalez, MD, PhD student, the Norwegian Centre for Movement Disorders, Stavanger University Hospital, found that baseline concentrations of plasma p-tau181 and p-tau231 were significantly higher in patients with LBD compared with healthy controls, but lower than those with AD and PD. When compared with normal marker levels, a subgroup of patients with LBD and abnormal cerebrospinal fluid (CSF) amyloid-ß42 (Aß42) levels had higher plasma concentrations of p-tau181 (difference between groups: –3.61 pg/mL [95% CI, –5.43 to –1.79]; P = .049) and p-tau231 (difference between groups: –2.51 pg/mL [95% CI, –3.63 to –1.39]; P = .02). 

No difference in levels of either p-tau markers were observed across confirmed AD pathologic characteristics based on reduced Aß42 level in CSF in individuals with LBD. A significant association was found between lower MMSE score at baseline and higher levels of p-tau181 (–0.092 MMSE points [95% CI, –0.12 to –0.06]; P = .001), as well as higher levels of p-tau231 (–0.16 MMSE points [95% CI, –0.21 to –0.12]; P <.001). 

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Higher levels of both markers were also associated with more rapid MMSE decline over time. After adjusting for sex and age in the longitudinal model (including the LBD subgroup with longitudinal measurements of cognition [n = 182] and a mean follow-up of 3.5 years [SD, 1.7]), investigators found that plasma p-tau181 concentration was associated with a decrease of –0.094 MMSE points each year (95% CI, –0.144 to –0.053; P = .02), and plasma p-tau231 concertation was associated with a decrease of –0.130 MMSE points each year (95% CI, –0.201 to –0.071; P = .02). 

Patients had a mean age of 70.0 years (standard deviation, 8.8). P-tau marker levels were measured by in-house single molecule array assays, while cognition was assessed with the Mini-Mental State Examination (MMSE). Overall, patients with LBD did not significantly differ in age, sex, or years of education from those in the AD group, but they were older than the healthy controls and had more men than both the healthy control and the AD groups.

A total of 1122 participants with plasma samples available were originally screened for the study. Patients were excluded in the event they had acute delirium or terminal illness, as well as if they had record of other previous psychiatric or neurologic disorders.

“To our knowledge, this is one of the largest DLB cohorts with biomarker data ever reported,” Gonzalez et al wrote, adding that there were some missing data for some variables due to the retrospective multicenter design, which led to reduced statistical power. Another limitation was noted as not all patients having a biomarker confirmation of diagnosis. “Future studies should compare p-tau species with other candidate blood biomarkers of progression (eg, Aβ42/40, neurofilament light chain, or glial fibrillary acidic protein) and explore their ability to assess prodromal DLB,” the authors added.

REFERENCE
Gonzalez MC, Ashton NJ, Gomes BF, et al. Association of Plasma p-tau181 and p-tau231 concentrations with cognitive decline in patients with probably dementia with Lewy bodies. JAMA Neurol. 2022;79(1):32–37. doi:10.1001/jamaneurol.2021.4222