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- Bettcher, B. M., et al.
(author)
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Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage
- 2018
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In: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 62:1, s. 385-397
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Journal article (peer-reviewed)abstract
- Inflammatory markers have been shown to predict neurocognitive outcomes in aging adults; however, the degree to which peripheral markers mirror the central nervous system remains unknown. We investigated the association between plasma and cerebrospinal fluid (CSF) markers of inflammation, and explored whether these markers independently predict CSF indicators of Alzheimer's disease (AD) pathology or neuronal damage. Plasma and CSF samples were analyzed for inflammatory markers in a cohort of asymptomatic older adults (n = 173). CSF samples were analyzed for markers of AD pathology (A beta(42), phosphorylated tau [p-tau], sA beta PP beta) or neuronal damage (total tau; neurofilament light chain) (n = 147). Separate linear models for each analyte were conducted with CSF and plasma levels entered simultaneously as predictors and markers of AD pathology or neuronal damage as outcome measures. Strong associations were noted between CSF and plasma MIP-1 beta levels, and modest associations were observed for remaining analytes. With respect to AD pathology, higher levels of plasma and CSF IL-8, CSF MIP-1 beta, and CSF IP-10 were associated with higher levels of p-tau. Higher levels of CSF IL-8 were associated with higher levels of CSF A beta(42). Higher CSF sA beta PP beta levels were associated with higher plasma markers only (IL-8; MCP-1). In terms of neuronal injury, higher levels of plasma and CSF IL-8, CSF IP-10, and CSF MIP-1 beta were associated with higher levels of CSF total tau. Exploratory analyses indicated that CSF A beta(42) modifies the relationship between plasma inflammatory levels and CSF tau levels. Results suggest that both plasma and CSF inflammatory markers independently relay integral information about AD pathology and neuronal damage.
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| 2. |
- Merluzzi, A. P., et al.
(author)
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Neurodegeneration, synaptic dysfunction, and gliosis are phenotypic of Alzheimer dementia
- 2018
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 91:5
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Journal article (peer-reviewed)abstract
- Objective To test the hypothesis that cognitively unimpaired individuals with Alzheimer disease (AD) neuropathology differ from individuals with AD dementia on biomarkers of neurodegeneration, synaptic dysfunction, and glial activation. In a cross-sectional study, adult participants >70 years old (n = 79, age 77.1 +/- 5.3 years) underwent comprehensive cognitive evaluation and CSF collection, which was assayed for markers of amyloid, phosphorylated tau (p-tau), neurodegeneration (neurofilament light protein [NFL] and total tau), synaptic dysfunction (neurogranin), and glial activation (chiti-nase-3-like protein 1 [YKL-40]). Participants were divided into 3 groups based on diagnosis and p-tau/beta-amyloid42 (A beta 42): those with low p-tau/A beta 42 and unimpaired cognition were classified as controls (n = 25); those with high p-tau/A beta 42 diagnosed with AD-dementia or AD-mild cognitive impairment were classified as AD-Dementia (n = 40); and those with high p-tau/A beta 42 but unimpaired cognition were classified as mismatches (n = 14). A similar, secondary analysis was performed with no age exclusion criteria (n = 411). In both the primary and secondary analyses, biomarker levels between groups were compared with the use of analysis of covariance while controlling for age and demographic variables. Despite p-tau/A beta 42 and A beta 42/A beta 40 levels comparable to those of the AD-Dementia group, mismatches had significantly lower levels of NFL and total tau. While not significantly lower than the AD-Dementia group on YKL-40 and neurogranin, mismatches were also not significantly different from controls. These results provide evidence that, in the absence of significant neurodegenerative processes, individuals who harbor AD neuropathology may remain cognitively unimpaired. This finding provides insight into the biological processes phenotypic of dementia and supports monitoring multiple biomarkers in individuals positive for AD neuropathology.
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