Markers of neuroinflammation associated with Alzheimer's disease pathology in older adults.

In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i.e. an AD CSF biomarker profile) and to investigate associations of inflammation markers with CSF biomarkers of amyloid, tau pathology, and neuronal injury. Cross-sectional analysis was performed on data from 120 older community-dwelling adults with normal cognition (n=48) or with cognitive impairment (n=72). CSF Aβ1-42, tau and p-tau181, and a panel of 37 neuroinflammatory markers in both CSF and serum were quantified. Least absolute shrinkage and selection operator (LASSO) regression was applied to determine a reference model that best predicts an AD CSF biomarker profile defined a priori as p-tau181/Aβ1-42 ratio >0.0779. It was then compared to a second model that included the inflammatory markers from either serum or CSF. In addition, the correlations between inflammatory markers and CSF Aβ1-42, tau and p-tau181 levels were assessed. Forty-two subjects met criteria for having an AD CSF biomarker profile. The best predictive models included 8 serum or 3 CSF neuroinflammatory markers related to cytokine mediated inflammation, vascular injury, and angiogenesis. Both models improved the accuracy to predict an AD biomarker profile when compared to the reference model. In analyses separately performed in the subgroup of participants with cognitive impairment, adding the serum or the CSF neuroinflammation markers also improved the accuracy of the diagnosis of AD pathology. None of the inflammatory markers correlated with the CSF Aβ1-42 levels. Six CSF markers (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the CSF tau and p-tau181 levels, and these associations remained significant after controlling for age, sex, cognitive impairment, and APOEε4 status. The identified serum and CSF neuroinflammation biomarker signatures improve the accuracy of classification for AD pathology in older adults. Our results suggest that inflammation, vascular injury, and angiogenesis as reflected by CSF markers are closely related to cerebral tau pathology.

Popp J ，Oikonomidi A ，Tautvydaitė D ，Dayon L ，Bacher M ，Migliavacca E ，Henry H ，Kirkland R ，Severin I ，Wojcik J ，Bowman GL ... -  《-》

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults.

Dayon L ，Wojcik J ，Núñez Galindo A ，Corthésy J ，Cominetti O ，Oikonomidi A ，Henry H ，Migliavacca E ，Bowman GL ，Popp J ... -  《-》

Decreasing body mass index is associated with cerebrospinal fluid markers of Alzheimer's pathology in MCI and mild dementia.

Several studies have identified an association between body mass index (BMI) and the incidence and severity of Alzheimer's disease (AD) but this relationship is not fully understood. The primary objective of this study was to assess the possible association between BMI and cerebrospinal fluid (CSF) biomarkers of AD pathology in subjects with normal cognition and cognitive impairment. The secondary objective was to test whether BMI may contribute to improve the accuracy of a clinical model to predict AD pathology in memory clinic patients with cognitive impairment. One hundred and seven elderly subjects with cognitive impairment (91 memory clinic patients with mild cognitive impairment [MCI] and 16 with dementia of AD type) and 55 cognitively healthy volunteers were included in this study. All subjects received a comprehensive clinical and neuropsychological evaluation and a lumbar puncture for CSF biomarker analysis. Multiple linear regressions and receiver operating characteristic (ROC) analyses were carried out to assess the association between BMI and the CSF biomarkers of AD pathology. BMI was positively correlated with the CSF levels of Aβ42 and negatively with tau and P-tau181 in participants with cognitive impairment. The associations were independent of age, sex, educational level, type and severity of cognitive impairment, cerebrovascular risk factors and the presence of the APOEε4 allele. Furthermore, BMI significantly improved the sensitivity and specificity of a multi-factorial model to predict the presence of an AD CSF biomarker profile. Lower BMI is associated with cerebral AD pathology rather than with cognitive impairment in elderly subjects with MCI and mild dementia. Along with other clinical factors, decreasing BMI may help the clinician to identify patients with cognitive impairment due to AD.

Mathys J ，Gholamrezaee M ，Henry H ，von Gunten A ，Popp J ... -  《-》

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.

Dayon L ，Guiraud SP ，Corthésy J ，Da Silva L ，Migliavacca E ，Tautvydaitė D ，Oikonomidi A ，Moullet B ，Henry H ，Métairon S ，Marquis J ，Descombes P ，Collino S ，Martin FJ ，Montoliu I ，Kussmann M ，Wojcik J ，Bowman GL ，Popp J ... -  《Alzheimers Research & Therapy》

Macrophage Migration Inhibitory Factor is Associated with Biomarkers of Alzheimer's Disease Pathology and Predicts Cognitive Decline in Mild Cognitive Impairment and Mild Dementia.

Oikonomidi A ，Tautvydaitė D ，Gholamrezaee MM ，Henry H ，Bacher M ，Popp J ... -  《-》