AUTHOR=Romo Eduardo Z. , Hong Brian V. , Patel Rishi Y. , Agus Joanne K. , Harvey Danielle J. , Maezawa Izumi , Jin Lee-Way , Lebrilla Carlito B. , Zivkovic Angela M. 

TITLE=Elevated lipopolysaccharide binding protein in Alzheimer’s disease patients with APOE3/E3 but not APOE3/E4 genotype

JOURNAL=Frontiers in Neurology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1408220

DOI=10.3389/fneur.2024.1408220

ISSN=1664-2295

ABSTRACT=<sec id="sec300"><title>Introduction</title><p>The role of lipopolysaccharide binding protein (LBP), an inflammation marker of bacterial translocation from the gastrointestinal tract, in Alzheimer’s disease (AD) is not clearly understood.</p></sec><sec id="sec301"><title>Methods</title><p>In this study the concentrations of LBP were measured in <italic>n</italic> = 79 individuals: 20 apolipoprotein E (APOE)3/E3 carriers with and 20 without AD dementia, and 19 <italic>APOE3/E4</italic> carriers with and 20 without AD dementia. LBP was found to be enriched in the 1.21–1.25 g/mL density fraction of plasma, which has previously been shown to be enriched in intestinally derived high-density lipoproteins (HDL). LBP concentrations were measured by ELISA.</p></sec><sec id="sec302"><title>Results</title><p>LBP was significantly increased within the 1.21–1.25 g/mL density fraction of plasma in <italic>APOE3/E3</italic> AD patients compared to controls, but not <italic>APOE3/E4</italic> patients. LBP was positively correlated with Clinical Dementia Rating (CDR) and exhibited an inverse relationship with Verbal Memory Score (VMS).</p></sec><sec id="sec303"><title>Discussion</title><p>These results underscore the potential contribution of gut permeability to bacterial toxins, measured as LBP, as an inflammatory mediator in the development of AD, particularly in individuals with the <italic>APOE3/E3</italic> genotype, who are genetically at 4-12-fold lower risk of AD than individuals who express <italic>APOE4</italic>.</p></sec>