The increase in TDP-43 and neurogranin blood levels at different stages of cognitive impairment in the elderly people: A cross-sectional study

BackgroundAlzheimer's disease (AD), a neurodegenerative condition and major subtype of dementia, is often preceded by mild cognitive impairment (MCI), a transitional stage before dementia. While cerebrospinal fluid (CSF) biomarkers are widely used for diagnosing AD and MCI, blood-based biomarkers offer the advantage of easier accessibility. This study aimed to compare blood levels of nine biomarkers among healthy controls, patients with MCI, and those with dementia, and to evaluate their potential for predicting AD progression.ObjectiveThe aim of our study was to study biomarkers in three groups of elderly people with varying degrees of cognitive decline.MethodsThe study included 234 participants aged 65 and older with dementia, MCI, or no cognitive impairment. Cognitive function was assessed using the Mini-Mental State Examination scale. Plasma levels of nine biomarkers, including amyloid-β₄₀ (Aβ₄₀), amyloid-β₄₂ (Aβ₄₂), KLK-6, NCAM-1, FGF-21, neurogranin, Tau, pTau181, and TDP-43, were measured by multiplex analysis.ResultsAβ₄₂ levels were higher in the MCI group compared to controls (p = 0.002) and in dementia patients compared to those with MCI (p = 0.018). TDP-43 and neurogranin levels were elevated in dementia patients compared to both the MCI group (p < 0.05 and p < 0.01, respectively) and controls (p < 0.05 and p < 0.001, respectively). Neurogranin levels were also higher in the MCI group compared to controls (p < 0.001) and significantly differed between MCI and dementia (p = 0.003).ConclusionsAβ₄₂, TDP-43, and neurogranin show potential as blood-based biomarkers for cognitive decline and may provide insight into the pathogenesis of neurodegeneration.