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.
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.
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.
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.
1. NIH/NINDS grant, RO1 AG042292, Co-Investigator, 2013- 2018. 2. California Department of Public Health, Co-Principle Investigator, 2016-2018.
Rotary Coins for Alzheimer?s Research Trust, Co- Investigator, 2016-2019.
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