LIPOPOLYSACCHARIDE AND E. COLI PROTEINS AND DNA IN ALZHEIMER’S DISEASE BRAINS COMPARED TO CONTROLS

Abstract

Amyloid plaques in Alzheimer's disease (AD) are believed to be derived in part from clevage products of amyloid precursor protein (APP). However, Gram-negative Escherichia coli (E. coli) bacteria and other microorganisms can form extracellular amyloid. Moreover, administration of Gram-negative bacterial derived Lipopolysaccharide (LPS) followed by ischemia and hypoxia produce plaque-like aggregates of myelin and amyloid ß in adult rat brains. These findings led us to examine human brain for LPS and E. coli proteins and DNA. Brain samples from superior temporal gyrus gray matter and frontal lobe white matter were studied from AD patients (n=24) and age-matched controls (n=18). LPS and E. coli proteins including K99 pili protein were evaluated by Western blots and immunocytochemistry. DNA from human brains was assessed for E. coli DNA. LPS and E. coli K99 were detected immunocytochemically in brain parenchyma and vessels in all AD and control brains. K99 levels by Western blots were greater in AD compared to control brains (p < 0.01) and K99 was localized to neurons in AD but not control brains. LPS co-localized with Aß1-40/42 in amyloid plaques and with Aß1-40/42 around vessels in AD brains. E. coli DNA or the E. coli K99 pili protein were detected in 9/10 control and 13/13 AD brains. LPS and E. coli bacterial proteins and DNA are found in control and AD brains. LPS co-localization with Aß1-40/42 in amyloid plaques and around vessels in AD brain suggest that LPS and/or other bacterial components could play a role in AD pathogenesis.