QUANTITATION OF THE BACTERIAL PRODUCT LIPOPOLYSACCHARIDE (LPS) IN POSTMORTEM SERUM AND BRAIN TISSUE FROM AD, MCI, AND CONTROL PATIENTS

Abstract

Aspects of Alzheimer's disease (AD) pathology suggest a microbial response. Studies indicate that Aβ may act as an anti-microbial peptide. 16S rRNA gene sequencing by our lab and others indicates that many kinds of bacteria are present in brain tissue from AD patients, and to some extent, in normal controls. As 16S analysis is sensitive to contamination and is non-quantitative, we sought a second to assess presence of bacteria in the brain. Lipopolysaccharide (LPS) has been previously localized within amyloid plaques. We quantified LPS from post-mortem serum and brain tissue to 1) confirm that LPS is present and 2) determine if LPS in the brain may originate from the bloodstream or instead indicate the presence of resident bacteria. Tissues were acquired from the Brain and Body Donation Program at the Banner Sun Health Research Institute. Post-mortem serum was tested for LPS by ELISA. Frozen tissue from the superior frontal gyrus of the same subjects was homogenized and sonicated in PBS to create lysates for ELISAs. There were four subject groups (n=12 per group): AD, MCI (mild cognitive impairment), HPC (high pathology controls), and normal non-demented controls. LPS was detected in the serum of most subjects at pg/ml levels. Average levels in AD subjects were significantly higher than in normal controls. In brain tissue, subjects from all groups showed easily detectable levels of LPS, primarily in the ng/ml range. Levels in serum did not correlate well with levels observed in the brain tissue from the same subjects. Our data shows the presence of substantial amounts of LPS in both serum and brain tissue from our MCI and AD subjects, and even in many normal controls. The disconnection of serum LPS levels from brain tissue levels may indicate that the bloodstream is not the primary source of LPS in the brain, although it is possible LPS from blood accumulates in the brain over time. However, given our previous 16s rRNA gene sequencing analysis of brain tissue from these same subjects, which showed DNA from a large variety of bacteria, the LPS most likely derives from resident bacteria in the brain.