A head‐to‐head comparison of plasma phosphorylated tau assays in the real‐world memory clinic

Abstract

BackgroundSeveral blood phosphorylated tau (P‐tau) species (P‐tau181, P‐tau217, and P‐tau231) have shown high accuracy to detect AD pathology, but a direct comparison of the main blood P‐tau assays in a real‐world memory clinic is needed. The main aim of this study is to perform a head‐to‐head comparison of 9 plasma Tau assays and determine their accuracy to discriminate between symptomatic AD from non‐AD.MethodThis is an observational and cross‐sectional study in the BIODEGMAR cohort, which includes patients presenting with cognitive complaints at the Cognitive Decline and Movement Disorders Unit of Hospital del Mar (Barcelona, Spain). Patients were classified into an AD CSF profile group or a non‐AD CSF profile group according to their CSF Aβ42/P‐tau181 ratio (Lumipulse, Fujirebio), and the discrimination accuracy of 9 plasma Tau assays was tested. All plasma samples were treated identically and measurements were performed in a blinded fashion.ResultA total of 197 participants (109 women [55.3%]; mean [SD] age, 72.3 [5.83] years), were investigated. All plasma Tau biomarkers were significantly higher in the AD CSF profile group than in the non‐AD CSF profile group. For plasma Tau biomarkers, the largest effect sizes were found in plasma Janssen P‐tau217 (r = 0.76), Lilly P‐tau217 (r = 0.73), ADx P‐tau181 (r = 0.73), Lilly P‐tau181 (r = 0.68), and UGot P‐tau231 (r = 0.63). All plasma Tau biomarkers significantly discriminated between patients with an AD CSF profile group from those with a non‐AD CSF profile. The AUC of plasma Tau biomarkers were the following (from highest to lower): Janssen P‐tau217 (0.96; 95% CI, 0.93‐0.99), ADx P‐tau181 (0.94; 95% CI, 0.91‐0.97) and Lilly P‐tau217 (0.94; 95% CI, 0.90‐0.98), Lilly P‐tau181 (0.91; 95% CI, 0.87‐0.96), UGot P‐tau231 (0.88; 95% CI, 0.83‐0.93), Quanterix P‐tau181 (0.80; 95% CI, 0.73‐0.87), UGot P‐tau181 (0.80; 95% CI, 0.73‐0.87), Lilly Total‐tau (0.73; 95% CI, 0.65‐0.81), and ADx P‐tau231 (0.66; 95% CI, 0.58‐0.74).ConclusionThe findings indicate that there are several plasma P‐tau biomarkers that can be used in a memory clinic setting as a stand‐alone biomarker to detect AD pathology in a diverse group of patients presenting with cognitive complaints.

The potential clinical value of plasma biomarkers in Alzheimer's disease

“…Plasma p‐tau and total tau (t‐tau) assays are also under investigation as potential triage tools. Several head‐to‐head studies have been conducted between a range of plasma p‐tau and t‐tau assays in a variety of cohorts and settings and report that p‐tau181, p‐tau217, and p‐tau231 are all promising plasma biomarkers for identifying people with Aβ pathology 28,31,61 . A 2021 study reported that plasma p‐tau231 levels increased earlier than plasma p‐tau181 levels, indicating that plasma p‐tau231 may be particularly useful for identifying symptomatic individuals who are early in the AD continuum 62 .…”

“…Several head-to-head studies have been conducted between a range of plasma p-tau and t-tau assays in a variety of cohorts and settings and report that p-tau181, p-tau217, and p-tau231 are all promising plasma biomarkers for identifying people with Aβ pathology. 28,31,61 A 2021 study reported that plasma p-tau231 levels increased earlier than plasma p-tau181 levels, indicating that plasma p-tau231 may be particularly useful for identifying symptomatic individuals who are early in the AD continuum. 62 Two further studies reported that p-tau231 increases and reaches abnormal levels at lower thresholds of brain amyloidosis than p-tau217 or p-tau181.…”

Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

“…In contrast, recent findings from multiple independent cohorts have shown that plasma p-tau biomarkers (p-tau181, p-tau217 and p-tau231) are strongly associated with both brain Aβ load 8–10 , the amounts and severity of tau pathology across the AD continuum 8 , and predict longitudinal changes in brain Aβ pathology 11 . Importantly, in contrast to plasma Aβ, high-performing p-tau immunoassays have a larger fold change (>100%) between Aβ-positive compared with Aβ-negative individuals especially in the advanced symptomatic stages 12 . Moreover, the plasma p-tau forms accurately identify an abnormal Aβ-PET scan 13 , a positive neuropathological diagnosis of AD at autopsy 14,15 , and predict longitudinal cognitive change 13 .…”

“…fold change (>100%) between Aβ-positive compared with Aβ-negative individuals especially in the advanced symptomatic stages 12 . Moreover, the plasma p-tau forms accurately identify an abnormal Aβ-PET scan 13 , a positive neuropathological diagnosis of AD at autopsy 14,15 , and predict longitudinal cognitive change 13 .…”

Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

“…In contrast, recent findings from multiple independent cohorts have shown that plasma p-tau biomarkers (p-tau181, p-tau217, and p-tau231) are strongly associated with both brain Aβ load 8 – 10 , the amounts and severity of tau pathology across the AD continuum 8 , and predict longitudinal changes in brain Aβ pathology 11 . Importantly, in contrast to plasma Aβ, high-performing p-tau immunoassays have a larger fold change ( > 100%) between Aβ-positive compared with Aβ-negative individuals, especially in the advanced symptomatic stages 12 . Moreover, the plasma p-tau forms accurately identify an abnormal Aβ-PET scan 13 , a positive neuropathological diagnosis of AD at autopsy 14 , 15 , and predict longitudinal cognitive change 13 .…”