English
As Alzheimer’s disease (AD) prevalence increases, identifying reliable biomarkers for diagnosis and monitoring is essential. This study investigates plasma biomarkers for tracking AD progression, specifically comparing rapid progressive Alzheimer’s dementia (rpAD) and non-rapid progressive Alzheimer’s dementia (non-rpAD). Biomarkers, including Tau, p-Tau 181, NfL, Aβ 1-42, Aβ 1-40, and the Aβ 42/40 ratio, were assessed for associations with disease stage, clinical progression, and cerebrospinal fluid (CSF) biomarkers. Longitudinal changes were analyzed to identify potential markers for distinguishing rpAD from non-rpAD and tracking disease dynamics over time.
Participants required to have AD-typical PET or CSF findings, an MMSE score below 30, and follow-up availability. Patients were classified as rpAD or non-rpAD based on an MMSE decline of six points within one year.
Plasma and CSF samples were collected, and biomarker concentrations were analyzed using Mann-Whitney U tests, logistic regression, and linear regression. Longitudinal biomarker changes were assessed using linear mixed-effects models.
In a cohort of 98 Alzheimer's patients, 23.5% exhibited rapid progression. At baseline, no significant differences were found in plasma biomarkers between rpAD and non-rpAD, although NfL showed a significant correlation with baseline MMSE (p=0.003). Plasma Aβ 1-40, Aβ 1-42, and CSF Aβ markers showed associations. Longitudinal analysis revealed significant increases in t-Tau (p=0.025), p-Tau 181 (p<0.001), Aβ 1-40 (p<0.001), and Aβ 1-42 (p<0.001) in the overall cohort. In rpAD, t-Tau, p-Tau 181, and Aβ 1-40 increased significantly (p=0.012, p=0.014, p=0.033), while NfL rose significantly in non-rpAD patients (p=0.005). No significant longitudinal changes were observed in Aβ 1-42 or Aβ 42/40 ratio between groups.
Our findings suggest that plasma biomarkers, particularly NfL, p-Tau 181, and Aβ 1-42, may serve as non-invasive indicators for monitoring AD progression, with potential for early diagnosis and disease tracking. While no significant differences were found between the rpAD and non-rpAD cohorts at baseline, longitudinal analysis revealed distinct biomarker dynamics, supporting the idea that tau biomarkers increase following rapid disease progression, while NfL may rise earlier. These biomarkers, particularly in plasma, hold promise for aiding diagnosis and tracking disease activity in Alzheimer’s disease. The observed correlation between plasma Aβ 1-42 and Aβ ratio with their cerebrospinal fluid counterparts further supports the potential of these biomarkers in reflecting pathological changes.
Keywords: Alzheimer's disease; Rapidly progressive Alzheimer's disease; Plasma biomarkers; Tau; p-Tau 181; NfL; Aβ 1-42; Aβ 1-40; Aβ 42/40 ratio
Persistent Address:
http://dx.doi.org/10.53846/goediss-11427
