Systemic brain derived neurotrophic factor but not intestinal barrier integrity is associated with cognitive decline and incident Alzheimer's disease

• Published in: PloS one 2021-03, Vol.16 (3), p.e0240342-e0240342
• Main Authors: Voigt, Robin M, Raeisi, Shohreh, Yang, Jingyun, Leurgans, Sue, Forsyth, Christopher B, Buchman, Aron S, Bennett, David A, Keshavarzian, Ali
• Format: Article
• Language: English
• Subjects: Age; Alzheimer's disease; Biology and Life Sciences; Biomarkers; Brain; Brain-derived neurotrophic factor; Cognition & reasoning; Cognitive ability; Complications and side effects; Cytokines; Dementia; Dementia disorders; Digestive system diseases; Disease; Editing; Education; Fatty acid-binding protein; Fatty acids; Funding; Genetic aspects; Health aspects; Health care facilities; Inflammation; Integrity; Internal medicine; Intestinal mucosa; Intestine; Lipopolysaccharides; Medicine; Medicine and Health Sciences; Memory; Methodology; Neurodegenerative diseases; Nutrition; Older people; Pathology; Phenotypes; Physiological aspects; Proteins; Risk factors; Social Sciences; Standard deviation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0240342

The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer's disease (AD) and Alzheimer's dementia. One potential source of inflammation is the intestine which harbors pro-inflammatory microorganisms capable of promoting neuroinflammation. Systemic inflammation is robustly associated with neuroinflammation as well as low levels of brain derived neurotrophic factor (BDNF) in the systemic circulation and brain. Thus, in this pilot study, we tested the hypothesis that intestinal barrier dysfunction precedes risk of death, incident AD dementia and MCI, cognitive impairment and neuropathology. Serum BDNF was associated with changes in global cognition, working memory, and perceptual speed but not risk of death, incident AD dementia, incident MCI, or neuropathology. Neither of the markers of intestinal barrier integrity examined, including lipopolysaccharide binding protein (LBP) nor intestinal fatty acid binding protein (IFABP), were associated with risk of death, incident AD dementia, incident mild cognitive impairment (MCI), change in cognition (global or domains), or neuropathology. Taken together, the data in this pilot study suggest that intestinal barrier dysfunction does not precede diagnosis of AD or MCI, changes in cognition, or brain pathology. However, since MCI and AD are related to global cognition, the findings with BDNF and the contiguous cognitive measures suggest low power with the trichotomous cognitive status measures. Future studies with larger sample sizes are necessary to further investigate the results from this pilot study.