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Neuroinflammation, cerebrovascular dysfunction and diurnal cortisol biomarkers in a memory clinic cohort: Findings from the Co-STAR study.
- Source :
-
Translational psychiatry [Transl Psychiatry] 2024 Sep 09; Vol. 14 (1), pp. 364. Date of Electronic Publication: 2024 Sep 09. - Publication Year :
- 2024
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Abstract
- Cortisol dysregulation, neuroinflammation, and cerebrovascular dysfunction are biological processes that have been separately shown to be affected in Alzheimer's disease (AD). Here, we aimed to identify biomarker signatures reflecting these pathways in 108 memory clinic patients with subjective cognitive decline (SCD, N = 40), mild cognitive impairment (MCI, N = 39), and AD (N = 29). Participants were from the well-characterized Cortisol and Stress in Alzheimer's Disease (Co-STAR) cohort, recruited at Karolinska University Hospital. Salivary diurnal cortisol measures and 41 CSF proteins were analyzed. Principal component analysis was applied to identify combined biosignatures related to AD pathology, synaptic loss, and neuropsychological assessments, in linear regressions adjusted for confounders, such as age, sex, education and diagnosis. We found increased CSF levels of C-reactive protein (CRP), interferon γ-inducible protein (IP-10), thymus and activation-regulated chemokine (TARC), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in MCI patients. Further, markers of cortisol dysregulation (flattened salivary cortisol awakening response and flattened cortisol slope) correlated with increased levels of placental growth factor (PlGF), IP-10, and chitinase 3-like 1 (YKL-40) in the total cohort. A biosignature composed of cortisol awakening response, cortisol slope, and CSF IL-6 was downregulated in AD patients. Moreover, biomarker signatures reflecting overlapping pathophysiological processes of neuroinflammation and vascular injury were associated with AD pathology, synaptic loss, and worsened processing speed. Our findings suggest an early dysregulation of immune and cerebrovascular processes during the MCI stage and provide insights into the interrelationship of chronic stress and neuroinflammation in AD.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Female
Male
Aged
Middle Aged
Cohort Studies
Circadian Rhythm physiology
Neuroinflammatory Diseases cerebrospinal fluid
C-Reactive Protein analysis
C-Reactive Protein metabolism
Intercellular Adhesion Molecule-1 metabolism
Vascular Cell Adhesion Molecule-1 metabolism
Neuropsychological Tests
Chemokine CXCL10 cerebrospinal fluid
Chemokine CXCL10 metabolism
Hydrocortisone metabolism
Biomarkers cerebrospinal fluid
Biomarkers metabolism
Cognitive Dysfunction cerebrospinal fluid
Cognitive Dysfunction metabolism
Alzheimer Disease metabolism
Alzheimer Disease cerebrospinal fluid
Saliva chemistry
Saliva metabolism
Cerebrovascular Disorders metabolism
Cerebrovascular Disorders cerebrospinal fluid
Subjects
Details
- Language :
- English
- ISSN :
- 2158-3188
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Translational psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 39251589
- Full Text :
- https://doi.org/10.1038/s41398-024-03072-x