Cerebrospinal fluid biomarkers including tau protein and amyloid-beta 42 for early detection and differential diagnosis of Alzheimer's disease

Abstract

In 1906, Alois Alzheimer first described the neuropathological hallmarks of the disease that now bears his name. More than a century later, early and accurate diagnosis remains a formidable clinical challenge. This research evaluated the diagnostic performance of cerebrospinal fluid (CSF) biomarkers, specifically total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and amyloid-beta 42 (Aβ42), for early detection and differential diagnosis of Alzheimer's disease (AD) across a cohort of 247 participants. The cohort included cognitively normal controls (n = 62), patients with mild cognitive impairment (MCI, n = 78), clinically diagnosed AD patients at varying severity stages (n = 83), and patients with non-AD dementias (n = 24). CSF t-tau and p-tau181 showed progressive elevation from cognitively normal through advanced AD stages, while Aβ42 demonstrated an inverse pattern with progressive decline. The combined biomarker panel achieved 94.3% sensitivity and 91.7% specificity for distinguishing AD from controls, and 87.8% sensitivity with 84.2% specificity for differentiating AD from non-AD dementias. These findings support the clinical implementation of CSF biomarker panels for early AD detection, particularly during the MCI stage when therapeutic interventions may have the greatest potential benefit.