Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.
Biomarkers
HDL
LDL
blood-brain barrier
cerebrospinal fluid
ptau
tau
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2022
2022
Historique:
pubmed:
7
2
2022
medline:
12
4
2022
entrez:
6
2
2022
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is a multifactorial process that takes years to manifest clinically. We propose that brain-derived indicators of cerebrovascular dysfunction and inflammation would inform on AD-related pathological processes early in, and perhaps prior to neurodegenerative disease development. Define the relationship between cerebrospinal fluid (CSF) markers of cerebrovascular dysfunction and neuroinflammation with AD CSF biomarkers in cognitively normal individuals. Analytes were measured from CSF and plasma collected at baseline from two randomized control trials. We performed Pearson correlation analysis (adjusting for age, sex, APOE haplotype, and education) between markers of central nervous system (CNS) barrier disruption, cerebrovascular dysfunction, CSF inflammatory cytokines and chemokines, and plasma lipid levels. We then developed a statistical prediction model using machine learning to test the ability of measured CSF analytes and blood lipid profiles to predict CSF AD biomarkers (total tau, phospho-tau (181), Aβ42) in this clinical population. Our analysis revealed a significant association between markers of CNS barrier dysfunction and markers of cerebrovascular dysfunction, acute inflammatory responses, and CSF inflammatory cytokines. There was a significant association of blood lipid profiles with cerebrovascular injury markers, and CSF inflammatory cytokine levels. Using machine learning, we show that combinations of blood lipid profiles, CSF markers of CNS barrier disruption, cerebrovascular dysfunction and CSF inflammatory cytokines predict CSF total tau, p-tau, and, to a lesser extent, Aβ42 in cognitively normal subjects. This suggests that these parallel pathological processes may contribute to the development of AD-related neuropathology in the absence of clinical manifestations.
Sections du résumé
BACKGROUND
Alzheimer's disease (AD) is a multifactorial process that takes years to manifest clinically. We propose that brain-derived indicators of cerebrovascular dysfunction and inflammation would inform on AD-related pathological processes early in, and perhaps prior to neurodegenerative disease development.
OBJECTIVE
Define the relationship between cerebrospinal fluid (CSF) markers of cerebrovascular dysfunction and neuroinflammation with AD CSF biomarkers in cognitively normal individuals.
METHODS
Analytes were measured from CSF and plasma collected at baseline from two randomized control trials. We performed Pearson correlation analysis (adjusting for age, sex, APOE haplotype, and education) between markers of central nervous system (CNS) barrier disruption, cerebrovascular dysfunction, CSF inflammatory cytokines and chemokines, and plasma lipid levels. We then developed a statistical prediction model using machine learning to test the ability of measured CSF analytes and blood lipid profiles to predict CSF AD biomarkers (total tau, phospho-tau (181), Aβ42) in this clinical population.
RESULTS
Our analysis revealed a significant association between markers of CNS barrier dysfunction and markers of cerebrovascular dysfunction, acute inflammatory responses, and CSF inflammatory cytokines. There was a significant association of blood lipid profiles with cerebrovascular injury markers, and CSF inflammatory cytokine levels. Using machine learning, we show that combinations of blood lipid profiles, CSF markers of CNS barrier disruption, cerebrovascular dysfunction and CSF inflammatory cytokines predict CSF total tau, p-tau, and, to a lesser extent, Aβ42 in cognitively normal subjects.
CONCLUSION
This suggests that these parallel pathological processes may contribute to the development of AD-related neuropathology in the absence of clinical manifestations.
Identifiants
pubmed: 35124650
pii: JAD215400
doi: 10.3233/JAD-215400
pmc: PMC10010435
mid: NIHMS1875513
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Cytokines
0
Peptide Fragments
0
tau Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
813-826Subventions
Organisme : RRD VA
ID : I01 RX001195
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066509
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG033693
Pays : United States
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