Biological determinants of blood-based cytokines in the Alzheimer's disease clinical continuum.
Alzheimer's disease
interleukin 10
interleukin 12
interleukin 1β
mild cognitive impairment
neuroinflammation
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
31
05
2022
received:
11
01
2022
accepted:
06
08
2022
pubmed:
12
8
2022
medline:
30
9
2022
entrez:
11
8
2022
Statut:
ppublish
Résumé
Converging translational and clinical research strongly indicates that altered immune and inflammatory homeostasis (neuroinflammation) plays a critical pathophysiological role in Alzheimer's disease (AD), across the clinical continuum. A dualistic role of neuroinflammation may account for a complex biological phenomenon, representing a potential pharmacological target. Emerging blood-based pathophysiological biomarkers, such as cytokines (Cyt) and interleukins (ILs), have been studied as indicators of neuroinflammation in AD. However, inconsistent results have been reported probably due to a lack of standardization of assays with methodological and analytical differences. We used machine-learning and a cross-validation-based statical workflow to explore and analyze the potential impact of key biological factors, such as age, sex, and apolipoprotein-E (APOE) genotype (the major genetic risk factor for late-onset AD) on Cyt. A set of Cyt was selected based on previous literature, and we investigated any potential association in a pooled cohort of cognitively healthy, mild cognitive impairment (MCI), and AD-like dementia patients. We also performed explorative analyses to extrapolate preliminary clinical insights. We found a robust sex effect on IL12 and an APOE-related difference in IL10, with the latter being also related to the presence of advanced cognitive decline. IL1β was the variable most significantly associated with MCI-to-dementia conversion over a 2.5 year-clinical follow-up. Although preliminary, our data support further clinical research to understand whether plasma Cyt may represent reliable and noninvasive tools serving the investigation of neuroimmune and inflammatory dynamics in AD and to foster biomarker-guided pathway-based therapeutic approaches, within the precision medicine development framework.
Substances chimiques
Apolipoproteins E
0
Biomarkers
0
Cytokines
0
Interleukin-10
130068-27-8
Interleukin-12
187348-17-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-52Informations de copyright
© 2022 International Society for Neurochemistry.
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