PMID- 26836182 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20220310 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 50 IP - 3 DP - 2016 TI - 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. PG - 873-86 LID - 10.3233/JAD-150897 [doi] AB - BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-beta (Abeta). 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 Abeta42 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 Abeta42 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. FAU - Melah, Kelsey E AU - Melah KE AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. FAU - Lu, Sharon Yuan-Fu AU - Lu SY AD - Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA. FAU - Hoscheidt, Siobhan M AU - Hoscheidt SM AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. FAU - Alexander, Andrew L AU - Alexander AL AD - Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA. FAU - Adluru, Nagesh AU - Adluru N AD - Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA. FAU - Destiche, Daniel J AU - Destiche DJ AD - Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA. FAU - Carlsson, Cynthia M AU - Carlsson CM AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. FAU - Zetterberg, Henrik AU - Zetterberg H AD - Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. AD - UCL Institute of Neurology, Queen Square, London, UK. FAU - Blennow, Kaj AU - Blennow K AD - Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden. FAU - Okonkwo, Ozioma C AU - Okonkwo OC AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Wisconsin Alzheimer's Institute, School of Medicine and Public Health, Madison, WI, USA. FAU - Gleason, Carey E AU - Gleason CE AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Dowling, N Maritza AU - Dowling NM AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. FAU - Bratzke, Lisa C AU - Bratzke LC AD - School of Nursing, Wisconsin School of Medicine and Public Health, Madison, WI, USA. FAU - Rowley, Howard A AU - Rowley HA AD - Department of Neuroradiology, School of Medicine and Public Health, Madison, WI, USA. FAU - Sager, Mark A AU - Sager MA AD - Wisconsin Alzheimer's Institute, School of Medicine and Public Health, Madison, WI, USA. FAU - Asthana, Sanjay AU - Asthana S AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Johnson, Sterling C AU - Johnson SC AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Wisconsin Alzheimer's Institute, School of Medicine and Public Health, Madison, WI, USA. AD - Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Bendlin, Barbara B AU - Bendlin BB AD - Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. AD - Wisconsin Alzheimer's Institute, School of Medicine and Public Health, Madison, WI, USA. LA - eng GR - UL1 TR000427/TR/NCATS NIH HHS/United States GR - R01 AG027161/AG/NIA NIH HHS/United States GR - P50 AG033514/AG/NIA NIH HHS/United States GR - R01 AG037639/AG/NIA NIH HHS/United States GR - P30 HD003352/HD/NICHD NIH HHS/United States GR - P30 HD003352-45/HD/NICHD NIH HHS/United States GR - UL1 RR025011/RR/NCRR NIH HHS/United States GR - R01 AG021155/AG/NIA NIH HHS/United States GR - R56 AG037639/AG/NIA NIH HHS/United States GR - 1UL1RR025011/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Netherlands TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Adipokines) RN - 0 (Amyloid beta-Peptides) RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CHI3L1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (Lectins) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-42)) RN - 0 (tau Proteins) SB - IM MH - Adipokines/cerebrospinal fluid MH - Aged MH - Alzheimer Disease/*cerebrospinal fluid/*pathology MH - Amyloid beta-Peptides/cerebrospinal fluid MH - Biomarkers/cerebrospinal fluid MH - Chemokine CCL2/cerebrospinal fluid MH - Chitinase-3-Like Protein 1 MH - Diffusion Tensor Imaging MH - Female MH - Hippocampus/pathology MH - Humans MH - Image Processing, Computer-Assisted MH - Lectins/cerebrospinal fluid MH - Male MH - Microglia/*pathology MH - Middle Aged MH - Peptide Fragments/cerebrospinal fluid MH - White Matter/*pathology MH - tau Proteins/cerebrospinal fluid PMC - PMC4760877 MID - NIHMS741177 OTO - NOTNLM OT - Alzheimer's disease OT - cerebrospinal fluid proteins OT - diffusion tensor imaging OT - inflammation EDAT- 2016/02/03 06:00 MHDA- 2016/11/01 06:00 PMCR- 2016/02/19 CRDT- 2016/02/03 06:00 PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2016/02/19 00:00 [pmc-release] AID - JAD150897 [pii] AID - 10.3233/JAD-150897 [doi] PST - ppublish SO - J Alzheimers Dis. 2016;50(3):873-86. doi: 10.3233/JAD-150897.