Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 50, Issue 3, Pages 873-886Publisher
IOS PRESS
DOI: 10.3233/JAD-150897
Keywords
Alzheimer's disease; cerebrospinal fluid proteins; diffusion tensor imaging; inflammation
Categories
Funding
- National Institute on Aging [R01 AG037639, R01 AG027161, ADRC P50 AG033514, R01 AG021155]
- University of Wisconsin Institute for Clinical and Translational Research
- National Center for Research Resources/National Institutes of Health Clinical and Translational Science Award [1UL1RR025011]
- program of the National Center for Research Resources, United States National Institutes of Health
- Waisman Center Core Grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development [P30 HD003352-45]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P30HD003352] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000427] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025011] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG021155, R56AG037639, R01AG027161, R01AG037639, P50AG033514] Funding Source: NIH RePORTER
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Background: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-beta (A beta). 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 A beta(42) and tau phosphorylated at threonine 181 (P-Tau(181)) 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 A beta(42) was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau(181) was associated with altered microstructure in precuneus. Conclusion: Inflammation may play a role in neural damage in preclinical AD.
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