Abstract
Background Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer‘s disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages.Methods In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having CSF AD (n=28, age=67, 33% female, Mini-mental state examination [MMSE]=28) or non-AD (n=24, age=70, 39% female, MMSE=27) profile based on the ratio between CSF total-tau (T-tau) and amyloid-β 1‐42 (Aβ 42 ) values (cut-off point chosen as 0.52). Novel CSF biomarkers included Neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and Glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assay (ELISA). Subjects underwent a neuropsychological assessment for evaluation of different cognitive domains including verbal episodic memory, non-verbal memory, language, processing speed and executive functions.Results Accuracy for distinguishing between the two CSF profiles was calculated for each CSF marker and cognitive domain. Verbal episodic memory performed the best overall (Area under curve [AUC]=0.80), with AUCs for CSF markers ranging from 0.61 to 0.64. For estimation of the relationships between CSF markers and cognitive domains (adjusted for age and education), Pearson‘s correlation and ridge regression analyses were performed. The ratio between NFL and YKL-40 levels correlated higher with verbal episodic memory score (r=-0.51, p <0.001) compared to single protein levels (NFL: r=-0.26, p =0.06; YKL-40: r=0.18, p =0.20). The correlation was also higher among those with CSF AD profile (r=-0.67, p <0.001) compared to those without (r=-0.46, p =0.03). GFAP levels showed weak correlation with executive functions scores (r=-0.37, p =0.007). Among those with a CSF AD profile, both S100B (r=-0.45, p =0.02) and GFAP (0.68, p <0.001) levels correlated with processing speed scores.ConclusionsThe novel CSF markers NFL, YKL-40 and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.
Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife