Plasma biomarker profiles and the association with cognitive function across the clinical spectrum of Alzheimer's disease

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AbstractBackgroundThe plasma biomarkers showed a promising value in the disease management of Alzheimer’s disease (AD). However, the profiles of the plasma biomarkers and the association with cognitive domains along the spectrum of AD have seldom been reported.MethodA total of 451 participants were recruited from a memory clinic cohort and a cohort with community‐dwellings. The global and domain‐specific neuropsychological tests were administrated in all participants. The Clinical Dementia Rating (CDR) was used to assess the severity of cognitive impairment. The diagnosis of mild cognitive impairment (MCI) and dementia were based on the Petersen’s criteria and DSM‐IV criteria. The AD was diagnosed according to the NINCDS‐ADRDA criteria. We described the continuum of AD based on the combination of CDR and the cognitive diagnosis: NC (CDR = 0), aMCI‐s (CDR = 0.5), aMCI‐m (CDR = 0.5), AD (CDR = 1), AD (CDR = 2), and AD (CDR = 3). The plasma Aβ 40, Aβ 42, Aβ 42/Aβ 40, t‐Tau, neurofilament protein light chain, and p‐Tau 181 were quantified using the Single molecule array platform. One‐way Analysis of Variance and Welch test were used for comparison among plasma markers. The association between domain z scores and log‐transformed plasma biomarker indexes were examined using partial Pearson correlation analysis with the adjustment for confounding variables.ResultThe concentration of plasma p‐Tau 181 basically increased along the clinical cognitive status, from normal cognition (CDR = 0) to AD (CDR = 3). There are varying degrees of correlation between six plasma biomarkers and different cognitive domains. Plasma p‐Tau 181 had the strongest correlation with MMSE (r = ‐0.494, P< 0.001), Memory (r = ‐0.417, P< 0.001), Attention (r = ‐0.388, P< 0.001), Visuospatial function (r = ‐0.328, P< 0.001), and Language (r = ‐0.123, P= 0.014). There was significant negative correlation between plasma p‐Tau 181 and four subgroups of cognitive domains, including MMSE in CDR >=1 group, Memory in CDR = 0.5 group & CDR >=1 group, and Attention in CDR >= 1 group.ConclusionPlasma p‐Tau 181 increased along the clinical continuum of AD, and had the strongest correlation with cognitive domains among all plasma biomarkers.