title: Gram-negative bacterial molecules associate with Alzheimer disease pathology.
abstract: OBJECTIVE
  We determined whether Gram-negative bacterial molecules are associated with Alzheimer disease (AD) neuropathology given that previous studies demonstrate Gram-negative Escherichia coli bacteria can form extracellular amyloid and Gram-negative bacteria have been reported as the predominant bacteria found in normal human brains.
  
  
  METHODS
  Brain samples from gray and white matter were studied from patients with AD (n = 24) and age-matched controls (n = 18). Lipopolysaccharide (LPS) and E coli K99 pili protein were evaluated by Western blots and immunocytochemistry. Human brain samples were assessed for E coli DNA followed by DNA sequencing.
  
  
  RESULTS
  LPS and E coli K99 were detected immunocytochemically in brain parenchyma and vessels in all AD and control brains. K99 levels measured using Western blots were greater in AD compared to control brains (p < 0.01) and K99 was localized to neuron-like cells in AD but not control brains. LPS levels were also greater in AD compared to control brain. LPS colocalized with Aβ1-40/42in amyloid plaques and with Aβ1-40/42around vessels in AD brains. DNA sequencing confirmed E coli DNA in human control and AD brains.
  
  
  CONCLUSIONS
  E coli K99 and LPS levels were greater in AD compared to control brains. LPS colocalized with Aβ1-40/42in amyloid plaques and around vessels in AD brain. The data show that Gram-negative bacterial molecules are associated with AD neuropathology. They are consistent with our LPS-ischemia-hypoxia rat model that produces myelin aggregates that colocalize with Aβ and resemble amyloid-like plaques.
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento. xzhan@ucdavis.edu.
authors: Xinhua
authors: X
authors: Zhan
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento.
authors: Boryana
authors: B
authors: Stamova
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento.
authors: Lee-Way
authors: LW
authors: Jin
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento.
authors: Charles
authors: C
authors: DeCarli
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento.
authors: Brett
authors: B
authors: Phinney
authors: From the Department of Neurology (X.Z., B.S., C.D., F.R.S.), MIND Institute (X.Z., B.S., F.R.S.), Alzheimer's Disease Center (L.-W.J., C.D.), Department of Pathology (L.-W.J.), and Proteomics Core Facility, Genome Center (B.P.), University of California at Davis, Sacramento.
authors: Frank R
authors: FR
authors: Sharp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D066128:Gray Matter / Q000098:blood supply / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D066127:White Matter / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)