학술논문
Longitudinal cerebrospinal fluid measurements show glial hypo- and hyperactivation in predementia Alzheimer’s disease
Document Type
article
Author
Kaja Nordengen; Bjørn-Eivind Kirsebom; Grit Richter; Lene Pålhaugen; Berglind Gísladóttir; Nikias Siafarikas; Arne Nakling; Arvid Rongve; Geir Bråthen; Gøril Rolfseng Grøntvedt; Fernando Gonzalez; Knut Waterloo; Kulbhushan Sharma; Thomas Karikari; Eleonora M. Vromen; Betty M. Tijms; Pieter J. Visser; Per Selnes; Milicia G. Kramberger; Bengt Winblad; Kaj Blennow; Tormod Fladby
Source
Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
1742-2094
Abstract
Abstract Background Brain innate immune activation is associated with Alzheimer’s disease (AD), but degrees of activation may vary between disease stages. Thus, brain innate immune activation must be assessed in longitudinal clinical studies that include biomarker negative healthy controls and cases with established AD pathology. Here, we employ longitudinally sampled cerebrospinal fluid (CSF) core AD, immune activation and glial biomarkers to investigate early (predementia stage) innate immune activation levels and biomarker profiles. Methods We included non-demented cases from a longitudinal observational cohort study, with CSF samples available at baseline (n = 535) and follow-up (n = 213), between 1 and 6 years from baseline (mean 2.8 years). We measured Aβ42/40 ratio, p-tau181, and total-tau to determine Ab (A+), tau-tangle pathology (T+), and neurodegeneration (N+), respectively. We classified individuals into these groups: A−/T−/N−, A+/T−/N−, A+/T+ or N+, or A−/T+ or N+. Using linear and mixed linear regression, we compared levels of CSF sTREM2, YKL-40, clusterin, fractalkine, MCP-1, IL-6, IL-1, IL-18, and IFN-γ both cross-sectionally and longitudinally between groups. A post hoc analysis was also performed to assess biomarker differences between cognitively healthy and impaired individuals in the A+/T+ or N+ group. Results Cross-sectionally, CSF sTREM2, YKL-40, clusterin and fractalkine were higher only in groups with tau pathology, independent of amyloidosis (p