Journal of Alzheimer's Disease
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Home > Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease.

TitleCerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsMelah, KE, Lu, SYuan-Fu, Hoscheidt, SM, Alexander, AL, Adluru, N, Destiche, DJ, Carlsson, CM, Zetterberg, H, Blennow, K, Okonkwo, OC, Gleason, CE, N Dowling, M, Bratzke, LC, Rowley, HA, Sager, MA, Asthana, S, Johnson, SC, Bendlin, BB
JournalJ Alzheimers Dis
Volume50
Issue3
Pagination873-86
Date Published2016
ISSN1875-8908
KeywordsAdipokines, Aged, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Chemokine CCL2, Chitinase-3-Like Protein 1, Diffusion Tensor Imaging, Female, Hippocampus, Humans, Image Processing, Computer-Assisted, Lectins, Male, Microglia, Middle Aged, Peptide Fragments, tau Proteins, White Matter
Abstract

BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-β (Aβ). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown.

OBJECTIVE: To determine whether neuroinflammation exacerbates neural damage in preclinical AD.

METHODS: We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI.

RESULTS: Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus.

CONCLUSION: Inflammation may play a role in neural damage in preclinical AD.

DOI10.3233/JAD-150897
Alternate JournalJ. Alzheimers Dis.
PubMed ID26836182
PubMed Central IDPMC4760877
Grant ListR01 AG037639 / AG / NIA NIH HHS / United States
P30 HD003352 / HD / NICHD NIH HHS / United States
UL1 TR000427 / TR / NCATS NIH HHS / United States
R01 AG027161 / AG / NIA NIH HHS / United States
P30 HD003352-45 / HD / NICHD NIH HHS / United States
UL1 RR025011 / RR / NCRR NIH HHS / United States
R01 AG021155 / AG / NIA NIH HHS / United States
1UL1RR025011 / RR / NCRR NIH HHS / United States
P50 AG033514 / AG / NIA NIH HHS / United States
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Source URL: https://www.j-alz.com/content/cerebrospinal-fluid-markers-alzheimers-disease-pathology-and-microglial-activation-are