Age-Dependent Relationship Between Plasma Aβ40 and Aβ42 and Total Tau Levels in Cognitively Normal Subjects

Abstract

Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer’s disease (AD). However, the constituents of these hallmarks, amyloid beta (Aβ) 40, Aβ42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age-dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups. A total of 391 cognitively normal subjects aged 23–91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating (CDR). We examined the effect of age on plasma levels of Aβ40, Aβ42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and Aβ42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = −0.126, p = 0.0128 for Aβ42), ranging from ages 23 to 91. Significant positive correlations were detected between Aβ42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between Aβ40 and t-Tau from age 40 to 91 (r ranged from −0.293 to −0.582) and between Aβ40 and Aβ42 in the age groups of 30–39 (r = −0.562, p = 0.0235), 50–59 (r = −0.261, p = 0.0142), 60–69 (r = −0.303, p = 0.0004), and 80–91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of Aβ42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between Aβ40, Aβ42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.

The Validation of Multifactor Model of Plasma Aβ42 and Total-Tau in Combination With MoCA for Diagnosing Probable Alzheimer Disease

“…Using Spearman correlation analysis, we found Aβ42 level is negatively correlated with age (r = −0.365, P = 0.005), and the value of Aβ42 × t-tau is negatively correlated with age (r = −0.266, P = 0.046) in the control group. These findings suggest that Aβ42 level as well as Aβ42 × t-tau value decreases according to age growth in healthy subjects, which agree with those of Lue et al (2019b), who showed that plasma Aβ42 decreased as age increased in cognitively normal subjects. These relationships provided evidence that Aβ42 may be involved in the pathophysiology of aging and could act as plasma biomarkers in aging-associated disease.…”

Plasma Biomarkers of Alzheimer’s Disease in African Americans

“…Higher plasma tau levels were also associated with older age in our study. These findings are consistent both with the notion that plasma tau is likely a biomarker of neurodegeneration [ 35 ] and that it is positively correlated with age [ 36 ]. We also identified association between older age and TNF α , as previously reported [ 30 ].…”

Classifications of Neurodegenerative Disorders Using a Multiplex Blood Biomarkers-Based Machine Learning Model

“…Age may influence the expressions of targeted proteins in the plasma. Plasma levels of the total Tau and Aβ42 levels have modest but significant correlations with chronological age [ 44 ] while there is no significant correlation between age and plasma α-synuclein levels in neurologically healthy controls [ 11 , 22 ]. This age effect was not considered in our machine-learning algorithm, and future classification models incorporating age effects are warranted.…”