Glial activation and inflammation along the Alzheimer's disease continuum

Abstract

Background: Neuronal and glial cell interaction is essential for synaptic homeostasis and may be affected in Alzheimer's disease (AD). We measured cerebrospinal fluid (CSF) neuronal and glia markers along the AD continuum, to reveal putative protective or harmful stage-dependent patterns of activation. Methods: We included healthy controls (n = 36) and Aβ-positive (Aβ+) cases (as defined by pathological CSF amyloid beta 1-42 (Aβ42)) with either subjective cognitive decline (SCD, n = 19), mild cognitive impairment (MCI, n = 39), or AD dementia (n = 27). The following CSF markers were measured: a microglial activation marker - soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a marker of microglial inflammatory reaction - monocyte chemoattractant protein-1 (MCP-1), two astroglial activation markers - chitinase-3-like protein 1 (YKL-40) and clusterin, a neuron-microglia communication marker - fractalkine, and the CSF AD biomarkers (Aβ42, phosphorylated tau (P-tau), total tau (T-tau)). Using ANOVA with planned comparisons, or Kruskal-Wallis tests with Dunn's pairwise comparisons, CSF levels were compared between clinical groups and between stages of biomarker severity using CSF biomarkers for classification based on amyloid pathology (A), tau pathology (T), and neurodegeneration (N) giving rise to the A/T/N score. Results: Compared to healthy controls, sTREM2 was increased in SCD (p