Gram-negative bacterial molecules associate with Alzheimer disease pathology

Research output: Contribution to journalArticle

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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 Aβ 1-40/42 in amyloid plaques and with Aβ 1-40/42 around 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 Aβ 1-40/42 in 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.

Original languageEnglish (US)
Pages (from-to)2324-2332
Number of pages9
JournalNeurology
Volume87
Issue number22
DOIs
StatePublished - Nov 29 2016

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Alzheimer Disease
Pathology
Brain
Lipopolysaccharides
Escherichia coli
Amyloid Plaques
DNA Sequence Analysis
Western Blotting
Bacteria
DNA
Myelin Sheath
Gram-Negative Bacteria
Amyloid
Ischemia
Immunohistochemistry
Neurons

ASJC Scopus subject areas

  • Clinical Neurology

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Gram-negative bacterial molecules associate with Alzheimer disease pathology. / Zhan, Xinhua; Stamova, Boryana; Jin, Lee-Way; DeCarli, Charles; Phinney, Brett; Sharp, Frank R.

In: Neurology, Vol. 87, No. 22, 29.11.2016, p. 2324-2332.

Research output: Contribution to journalArticle

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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 Aβ 1-40/42 in amyloid plaques and with Aβ 1-40/42 around 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 Aβ 1-40/42 in 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.",
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AU - Sharp, Frank R

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