Serum biomarkers as prognostic markers for Alzheimer's disease in a clinical setting

Blood-based glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (pTau) have shown promising prognostic potential in Alzheimer's disease (AD), but their applicability in clinical settings where comorbidities are prevalent remains uncertain.

Simoa assays quantified GFAP, NfL, and pTau181 in retrospectively retrieved prediagnostic serum samples from 102 AD patients and 21 non-AD controls.

Higher serum GFAP levels predicted earlier clinical presentation and faster subsequent Mini-Mental State Examination decline in AD patients. Serum NfL levels were increased in patients with arterial hypertension (AHT), kidney dysfunction, and a history of stroke and only demonstrated predictive value for time to clinical AD presentation after adjustment for these comorbidities. Serum pTau181 instability during long-term storage at -20°C prevented its prognostic evaluation in retrospectively retrieved serum samples.

Serum GFAP is a robust prognostic marker for AD progression, whereas NfL is impacted by various comorbidities, which complicates the interpretation of its prognostic value.

Serum GFAP levels predict time to clinical AD presentation.Serum NfL levels are increased by hypertension, kidney disease, and stroke history.Prognostic value of serum NfL in AD is only evident after comorbidity correction.Serum levels of GFAP, but not NfL, increase over time within prediagnostic AD stages.