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The following is a summary of “Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term, randomised trial,” published in the December 2024 issue of Neurology by Soldan et al.
Blood-based biomarkers of amyloid and tau predict Alzheimer’s disease (AD) dementia, but the role in predicting mild cognitive impairment (MCI) is less understood.
Researchers conducted a prospective study to examine if blood biomarkers of amyloid (Aβ42 /Aβ40 ratio), tau (p-tau181), neurodegeneration (NfL), and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) predict the onset of in people with MCI who were cognitively normal at the start.
They studied participants from the longitudinal observational BIOCARD study who provided plasma samples at baseline and approximately 7 years later. Plasma biomarkers analyzed included amyloid (Aβ42 /Aβ40 ratio), tau (p-tau181), NfL, and neuroinflammation using the NeuroToolKit. Cox regression models tested associations of biomarker levels with time to MCI onset.
The results showed 271 individuals at baseline 1, mean age 57.5 years, 60.5% female, 82 progressed to MCI; 202 at baseline 2, mean age 64.5 years, 62.4% female, 31 progressed to MCI lower plasma Aβ42 /Aβ40 ratio (both HRs ≤ 0.69, 95%CIs ≤ 0.55–0.87, P≤ 0.034), higher GFAP (HRs ≥ 1.83, CIs ≥ 1.28–2.60, P<0.002), and a higher ratio of p-tau181 /(Aβ42 /Aβ40) (HRs ≥ 1.64, CIs ≥ 1.25–2.13, P≤0.001) were associated with earlier MCI symptom onset for both baseline 1 and baseline 2. For baseline 2, higher p-tau181 (HR = 2.07, CI = 1.12–3.83, P=0.021) and higher NfL (HR = 1.75, CI = 0.99–3.10, P=0.05) were linked with earlier MCI onset within 7 years. When combining biomarkers, neither GFAP nor NfL were linked with MCI onset after accounting for AD biomarkers, where p-tau181 /(Aβ42 /Aβ40) remained significant, YKL40 and sTREM2 were not associated with MCI onset.
They concluded that blood biomarkers of Aβ42 /Aβ40 ratio), tau (p-tau181), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP] were linked to earlier MCI onset, with amyloid and tau biomarkers being the most predictive. However, NfL markers like NfL were not associated with MCI onset after adjusting for amyloid and tau levels.
Source: neurology.org/doi/10.1212/WNL.0000000000210225
