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• W2897860076 abstract "Amyloid-beta (Aβ) is one of the earliest markers for Alzheimer's disease (AD) and apolipoprotein E (APOE) ε4 carriership is the strongest genetic AD risk factor. The relationship between Aβ, APOE-ε4 and cognition, with emerging cerebrospinal fluid (CSF) markers YKL-40, neurogranin (Ng) and neurofilament light (NFL), across the clinical AD spectrum, remains uncertain. We included 770 individuals from the EMIF-AD Multimodal Biomarker Discovery study - a cohort collated from 3 multicenter and 8 single center European studies - for whom CSF analyses were conducted centrally. 140 individuals were cognitively normal (CN), 450 had mild cognitive impairment (MCI) and 180 had AD dementia. The CSF Aβ42/40 ratio, with a cohort specific cut-off (0.061), was used to determine Aβ status. We compared characteristics within diagnostic group by Aβ status using ANOVA and Chi-square. Linear mixed modeling was used to compare NFL, Ng and YKL-40 concentrations by APOE-ε4 status and to test the influence of these markers on cognition, all stratified by Aβ status and adjusted for demographics and study. Compared to Aβ- individuals, Ng levels were elevated in Aβ+ individuals across the AD spectrum, while NFL and YKL levels were only elevated in Aβ+ CN and MCI individuals. In Aβ- individuals with MCI or AD-type dementia, APOE ε4+ was associated with decreased levels of NFL and Ng. High NFL was associated with lower cognitive performance at baseline and a faster rate of decline, regardless of Aβ status (Figure 1). High Ng was also associated with a faster rate of decline, regardless of Aβ, but only in the dementia stage. High YKL-40 was associated with lower baseline scores and a faster rate of decline only in Aβ- individuals (Figure 1). NFL is an early diagnostic and prognostic neurodegenerative marker, but non-specific for AD. Ng is a valuable diagnostic AD marker as it is associated with Aβ in all cognitive stages. As YKL-40 has been indentified as inflammation marker previously, our findings suggest that Aβ pathology is associated with inflammation in the pre-dementia stages and this may influence cognition in absence of Aβ. These findings are of value in clinical practice, trial recruitment and research." @default.
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• W2897860076 date "2018-07-01" @default.
• W2897860076 modified "2023-10-18" @default.
• W2897860076 title "F1‐02‐01: RELATING CSF MARKERS NEUROGRANIN, NEUROFILAMENT‐LIGHT AND YKL‐40 TO Aβ, APOE ε4 AND COGNITION: RESULTS FROM THE EMIF‐AD MULTIMODAL BIOMARKER DISCOVERY STUDY" @default.
• W2897860076 doi "https://doi.org/10.1016/j.jalz.2018.06.2307" @default.
• W2897860076 hasPublicationYear "2018" @default.
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