Biomarkers - Part 1.

Abstract

The CSF amyloid to tau ratio can isolate cognitively healthy participants into normal Aβ42/tau (CH-NAT) or a pathological Aβ42/tau (CH-PAT) with a low or high risk of cognitive decline, respectively. We aim to determine if plasma Aβ42/tau ratios can differentiate CH-NAT from CH-PAT participants. Study participants (> 65 years of age) were recruited, and demographic, neurological, and neuropsychological data were obtained in an ongoing HMRI Brain Aging study. Overnight fasting plasma and CSF were collected within a month of examination, and the levels of Aβ38, Aβ40, Aβ42 (MSD 6E10 kit), and total tau were quantified using the MSD electrochemiluminescence platform. Differences in fluid biomarker levels and the plasma ratios (n = 55) and CSF ratios (Aβ42/Aβ40, n = 41, Aβ42/tau, n = 55) were determined using nonparametric student t-test and correlations using a Spearman test. Aβ40 and Aβ42 levels were higher (15-18-fold, and 10-14-fold, respectively), while tau levels are 8-13-fold higher in CSF than in plasma. Plasma and CSF Aβ40 were not distinct in CH-NAT compared with CH-PAT. In contrast, Aβ42 levels were 30.9% lower in CH-PAT (16.3 ± 18.3 pg/ml) compared with CH-NAT plasma (23.6 ± 26.4 pg/mL) (p < 0.05). CSF Aβ42 levels in CH-PAT (171.6 ± 124.6 pg/mL) were lower by 47.6% compared with CH-NAT (327.6 ± 182.6 pg/ml) (p < 0.0001). The Aβ42/Aβ40 ratio was significantly lower in both plasma and CSF (Table 1A). Similarly, the Aβ42/tau ratio was significantly lower in plasma and CSF (Table 1B). Individually, plasma levels of Aβ42 and tau did not correlate with CSF levels. However, the ratio of Aβ42 to total tau in plasma significantly correlated with the CSF ratios (Spearman r = 0.36, p = 0.0071). Finally, CSF Aβ42/Aβ40 ratio correlated with Aβ42/tau ratio for all samples, CH (n = 100) and MCI (n = 35) (Fig. 1). While not as robust as CSF ratios, plasma Aβ42/Aβ40 and Aβ42/tau ratios can isolate cognitively healthy participants with lower risk from participants with a higher risk of cognitive decline. Thus, plasma represents a less invasive medium for the biomarker classification of aging participants.