Plasma Core Alzheimer’s Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline

Abstract

Blood-based biomarkers have been considered as a promising method for the diagnosis of Alzheimer’s disease (AD). The reliability and accuracy of plasma core AD biomarkers, including phosphorylated tau (P-tau181), total tau (T-tau), Aβ42, and Aβ40, have also been confirmed in diagnosing AD and predicting cerebral β-amyloid (Aβ) deposition in Western populations, while fewer research studies have ever been conducted in China’s Han population. In this study, we investigated the capability of plasma core AD biomarkers in predicting cerebral Aβ deposition burden among the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort consisting of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer’s dementia disease (Non-ADD). Body fluid (plasma and CSF) AD core biomarkers were measured via single-molecule array (Simoa) immunoassay. The global standard uptake value ratio (SUVR) was then calculated by 18F-florbetapir PET, which was divided into positive (+) and negative (−). The most significant correlation between plasma and CSF was plasma P-tau181 (r = 0.526, P < 0.0001). Plasma P-tau181 and P-tau181/T-tau ratio were positively correlated with global SUVR (r = 0.257, P < 0.0001; r = 0.263, P < 0.0001, respectively), while Aβ42 and Aβ42/Aβ40 ratio were negatively correlated with global SUVR (r = −0.346, P < 0.0001; r = −0.407, P < 0.0001, respectively). Interestingly, voxel-wise analysis showed that plasma P-tau181 and P-tau181/T-tau ratio were negatively related to 18F-florbetapir PET in the hippocampus and parahippocampal cortex. The optimal predictive capability in distinguishing all Aβ+ participants from Aβ– participants and MCI+ from MCI– subgroups was the plasma P-tau181/T-tau ratio (AUC = 0.825 and 0.834, respectively). Our study suggested that plasma P-tau181 and P-tau181/T-tau ratio possessed better diagnostic and predictive values than plasma Aβ42 and Aβ42/Aβ40 in this cohort, a finding that may be useful in clinical practices and trials in China.

Novel β-amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline

“…The results showed that Aβ 42 and the Aβ 42 /Aβ 40 ratio exhibited a negative correlation with global SUVR, while P-tau181 and the P-tau181/T-tau ratio displayed a positive correlation with global SUVR. These findings align with our previous research on the relationships between global SUVR from [ 18 F]Florbetapir PET and plasma AD biomarkers in a cohort study on dementia population . Currently, it is reported that commercially available Aβ PET were correlationed with plasma AD biomarkers, and Aβ42/40 and P-tau181 demonstrated higher agreement with PET findings. − Therefore, the results of our study also validate the reliability of [ 18 F] 92 from this perspective.…”

Predicting amyloid‐PET and clinical conversion in apolipoprotein E ε3/ε3 non‐demented individuals with multidimensional factors

“…Plasma p‐tau 181 as a candidate biomarker, can predict Aβ pathology and cognitive decline (Karikari et al, 2020; Mielke et al, 2018). It can also identify Aβ‐PET (+) individuals (including those with clinical diagnosis of CN, MCI, or dementia) because of its high specificity for Aβ plaque pathology (Barthélemy et al, 2020; Ni et al, 2023). When plasma p‐tau 181 is combined with other clinical information, Aβ (+) can also be detected during the CN and MCI phase (Tosun et al, 2021).…”

Plasma p‐tau217, p‐tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study

“…Previous studies found plasma p-tau217 and p-tau181 were associated with amyloid PET, 16,36,[41][42][43][44] and could distinguish Aβ+ from Aβ-, 11,14,16,23,36,[45][46][47][48] which implied that plasma p-tau reflected the brain amyloid pathology. Comparing to plasma p-tau181, p-tau217 could more accurately distinguish Aβ+ from Aβ-in community residents in the MCSA.…”