Neuroinflammatory phenotype in early Alzheimer's disease

Tiffany L. Sudduth, Frederick A. Schmitt, Peter T. Nelson, Donna M. Wilcock

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Alzheimer's disease (AD) involves progressive neurodegeneration in the presence of misfolded proteins and poorly-understood inflammatory changes. However, research has shown that AD is genetically, clinically, and pathologically heterogeneous. In frozen brain samples of frontal cortex (diseased) and cerebellum (nondiseased) from the University of Kentucky Alzheimer's Disease Center autopsy cohort, we performed gene expression analysis for genes categorizing inflammatory states (termed M1 and M2) from early and late stage AD, and age-matched nondemented controls. We performed analysis of the serum samples for a profile of inflammatory proteins and examined the neuropathologic data on these samples. Striking heterogeneity was found in early AD. Specifically, early-stage AD brain samples indicated apparent polarization toward either the M1 or M2 brain inflammatory states when compared with age-matched nondisease control tissue. This polarization was observed in the frontal cortex and not in cerebellar tissue. We were able to detect differences in AD neuropathology, and changes in serum proteins that distinguished the individuals with apparent M1 versus M2 brain inflammatory polarization.

Original languageEnglish
Pages (from-to)1051-1059
Number of pages9
JournalNeurobiology of Aging
Volume34
Issue number4
DOIs
StatePublished - Apr 2013

Bibliographical note

Funding Information:
The project described was supported in part by NIH grant P30 AG028383 and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health , through Grant UL1RR033173 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors thank all of the study volunteers, and Sonya Anderson, Ela Patel, and Erin Abner for technical support, Greg Cooper, MD, Greg Jicha, MD, Charles Smith, MD, Nancy Stiles, MD, and Alison Cabat-Holt, PhD, for the clinical evaluations, Daron Davis, MD, and Stephen W. Scheff, PhD, for pathologic evaluations, and Richard Kryscio, PhD, for statistical consultation.

Keywords

  • Alzheimer's
  • Clinical trials
  • Cytokines
  • Inflammation
  • Microglia

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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