Dataset Information

Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.

ABSTRACT:

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.

SUBMITTER: Jansson D

PROVIDER: S-EPMC10010435 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.

Jansson Deidre D Wang Marie M Thomas Ronald G RG Erickson Michelle A MA Peskind Elaine R ER Li Ge G Iliff Jeffrey J

Journal of Alzheimer's disease : JAD 20220101 2

<h4>Background</h4>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.<h4>Objective</h4>Define the relationship between cerebrospinal fluid (CSF) markers of cerebrovascular dysfunction and neuroinflammation with AD CSF biomarkers in cognitively norm ...[more]

PMID: 35124650

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Project description:In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Dataset Information

Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.

Background

Objective

Methods

Results

Conclusion

Publications

Markers of Cerebrovascular Injury, Inflammation, and Plasma Lipids Are Associated with Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Cognitively Normal Persons.

Similar Datasets

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