Is amyloid involved in acute neuroinflammation? A CSF analysis in encephalitis

Abstract

Introduction: Several investigations have argued for a strong relationship between neuroinflammation and amyloid metabolism but it is still unclear whether inflammation exerts a pro-amyloidogenic effect, amplifies the neurotoxic effect of amyloid, or is protective.

Methods: Forty-two patients with acute encephalitis (ENC) and 18 controls underwent an extended cerebrospinal fluid (CSF) panel of inflammatory, amyloid (Aβ40, 42, and 38, sAPP-α, sAPP-β), glial, and neuronal biomarkers. Linear and non-linear correlations between CSF biomarkers were evaluated studying conditional independence relationships.

Results: CSF levels of inflammatory cytokines and neuronal/glial markers were higher in ENC compared to controls, whereas the levels of amyloid-related markers did not differ. Inflammatory markers were not associated with amyloid markers but exhibited a correlation with glial and neuronal markers in conditional independence analysis.

Discussion: By an extensive CSF biomarkers analysis, this study showed that an acute neuroinflammation state, which is associated with glial activation and neuronal damage, does not influence amyloid homeostasis.

Keywords: acute inflammation; amyloid; glial cells; neuroinflammation; tau.

FIGURE 1

Estimated probability of connection between biomarkers according to the non‐linear model. β2M, β2‐microglobulin; GFAP, glial fibrillary acidic protein; IL‐6, interleukin 6; IL‐8, interleukin 8; NfL, neurofilament light chain; p‐tau, phosphorylated tau; sAPP‐α, soluble amyloid precursor protein alpha, sAPP‐β, soluble amyloid precursor protein beta; sTREM‐2, triggering receptor expressed on myeloid cells 2; TNF‐α, tumor necrosis factor alpha; t‐tau, total Tau protein; YKL‐40, chitinase‐3‐like protein

FIGURE 2

Graphical representation of estimated probability of connection in encephalitis obtained by fixing the position of the nodes using a Fruchterman–Reingold force‐direct algorithm. The edges’ thicknesses are proportional to the estimated probabilities of connection. Values below the prior expected value of 0.25 are not reported for graphical purposes. β2M, β2‐microglobulin; GFAP, glial fibrillary acidic protein; IL‐1β, interleukin‐1β; IL‐6, interleukin 6; IL‐8, interleukin 8; NfL, neurofilament light chain; p‐tau, phosphorylated tau; sAPP‐α, soluble amyloid precursor protein alpha, sAPP‐β, soluble amyloid precursor protein beta; sTREM‐2, triggering receptor expressed on myeloid cells 2; TNF‐α, tumor necrosis factor alpha; t‐tau, total tau protein; YKL‐40, chitinase‐3‐like protein 1