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Kirsebom, Bjørn Eivind; Nordengen, Kaja; Selnes, Per; Torsetnes, Silje Bøen; Sharma, Kulbhushan; Gisladottir, Berglind; Fladby, Tormod

Sex differences of innate immune activation in amyloid positive predementia cases : Molecular and cell biology/neuroinflammation : Molecular and cell biology/neuroinflammation

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  • Medientyp: E-Artikel
  • Titel: Sex differences of innate immune activation in amyloid positive predementia cases : Molecular and cell biology/neuroinflammation : Molecular and cell biology/neuroinflammation
  • Beteiligte: Kirsebom, Bjørn Eivind; Nordengen, Kaja; Selnes, Per; Torsetnes, Silje Bøen; Sharma, Kulbhushan; Gisladottir, Berglind; Fladby, Tormod
  • Erschienen: Wiley, 2020
  • Erschienen in: Alzheimer's & Dementia
  • Sprache: Englisch
  • DOI: 10.1002/alz.046464
  • ISSN: 1552-5279; 1552-5260
  • Schlagwörter: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>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 <jats:italic>APOE‐ε4</jats:italic> interactions with sex and CSF Aβ.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>Significant interaction effects between sex and CSF Aβ status showed lower CSF YKL‐40 (p&lt;.001), sTREM2 (p&lt;.05) and MCP‐1 (p&lt;.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&lt;.001), sTREM2 (p&lt;.05) and MCP‐1 (p&lt;.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 <jats:italic>APOE‐ε4</jats:italic> were found.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We found consistent differences in innate immune activation in Aβ+ females, but not related to <jats:italic>APOE‐</jats:italic>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.</jats:p></jats:sec>