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Sex differences of innate immune activation in amyloid positive predementia cases
Author(s) -
Kirsebom Bjørn Eivind,
Nordengen Kaja,
Selnes Per,
Torsetnes Silje Bøen,
Sharma Kulbhushan,
Gisladottir Berglind,
Fladby Tormod
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046464
Subject(s) - innate immune system , neurodegeneration , medicine , cohort , sexual dimorphism , cerebrospinal fluid , sex characteristics , immune system , disease , dementia , serum amyloid a , endocrinology , immunology , inflammation
Background Innate immunity is linked to Alzheimer’s disease, as shown by genome‐wide association studies and experimental data. There is, however, a sexual dimorphism in the activation of the innate immune system. Here, we investigate sex‐differences in immune activation by comparing glial activation markers in CSF from males and females with amyloid pathology as compared to healthy controls. Method A total of 110 CSF Aβ‐ healthy controls (n=52 males and n=58 females), and 121 CSF Aβ+ (n=70 males and n=51 females) non‐demented cases with cognitive symptoms from the Dementia Disease Initiation (DDI) cohort were included in the analyses. CSF levels of sTREM2, YKL‐40 and MCP‐1 were determined using Mesoscale Discovery. Amyloid pathology was determined using CSF Aβ1‐42 threshold of 708 pg/mL. CSF total tau was included in our models to investigate potential sex differences of active neurodegeneration. We compared CSF concentrations using three‐way ANCOVA with age as a covariate, investigating main effects, two‐way interaction effects between sex and CSF Aβ status and three‐way APOE‐ε4 interactions with sex and CSF Aβ. Result Significant interaction effects between sex and CSF Aβ status showed lower CSF YKL‐40 (p<.001), sTREM2 (p<.05) and MCP‐1 (p<.0001) levels in Aβ+ women as compared to males. No differences in levels were found between male and female healthy controls. Furthermore, we found that only Aβ+ males had increased YKL‐40 (p<.001), sTREM2 (p<.05) and MCP‐1 (p<.05) levels compared to healthy controls, whilst Aβ+ females showed no significant differences in levels. Men had slightly higher levels of CSF total tau as compared to women, however, this difference did not reach the threshold for statistical significance (p=.07). No main effects or interaction effects with APOE‐ε4 were found. Conclusion We found consistent differences in innate immune activation in Aβ+ females, but not related to APOE‐ ε4 genotype. However, a slight non‐significant increase in a CSF marker of neurodegeneration in men may in part contribute to the observed differences in immune activation in our sample. The low level of innate immune activation has yet to be linked to differences in disease progression.