Group 4 - Helicobacter infection and Alzheimer’s disease (PI: Claire Roubaud-Baudron)
Alzheimer’s disease (AD) is the leading cause of disabilities and concerns more than 800,000 patients in France. Unfortunately, treatments based on the amyloid hypothesis are disappointing. There is a growing body of evidence that amyloid beta peptide, a histopathological hallmark of AD, could act like an antimicrobial peptide, supporting the infectious hypothesis of AD. Moreover, the neuroinflammation plays a very important role in AD pathology. H. pylori infection induces a life-long gastritis which remains asymptomatic in 90% of cases and may influences AD’s course by vascular and inflammatory mechanisms.
In collaboration with the Bordeaux Population Health Centre (ISPED INSERM 1219), we carried out an ancillary study on 500 subjects and found that H. pylori infection was associated with an increased AD incidence after controlling for other AD risk factors (manuscript in preparation). These results confirmed a previous study on an older cohort (30 years apart) (Roubaud Baudron et al. J Am Geriatr Soc 2013). Because of the possibility of confounding factors, we used a murine model of infection with H. pylori. Mice predisposed to AD (transgenic mice) infected by H. pylori presented an increased number of amyloid plaques in their brains compared to non-infected mice (manuscript in preparation). We also found that H. pylori infection in wild type (WT) mice did not induce amyloid plaques but increased neuroinflammation without an increased systemic inflammation (Albaret et al. JAD 2019). The association between the two diseases could be explained by the nervous system (stomach brain axis) and deserves more research.
5 main publications
1- Roubaud Baudron C, Varon C, Mégraud F, Salles N. Alzheimer's disease: the infectious hypothesis. Geriatr Psychol Neuropsychiatr Vieil. 2015 Dec;13(4):418-24. Review. French.
1- Baudron CR, Chambonnier L, Giese A, Buissionnière A, Macrez N, Cho Y, Fénelon V, Blaszczyk L, Dubus P, Lehours P, Mégraud F, Salles N, Varon C. An eighteen months Helicobacter infection does not induce amyloid plaque nor neuroinflammation in brains of wild type C57BL/6J mice. Journal of Alzheimer’s Disease 2015;45(4):1045-50. (IF 3.909)
2- Roubaud Baudron C, Varon C, Mégraud F, Salles N. Alzheimer's disease: the infectious hypothesis. Geriatr Psychol Neuropsychiatr Vieil. 2015 Dec;13(4):418-24. Review. French.
3- Franceschi F, Covino M, Roubaud Baudron C. Review: Helicobacter pylori and extragastric diseases. Helicobacter. 2019 Sep;24 Suppl 1:e12636. (IF 4.123)
4- Roubaud-Baudron C, Mégraud F, Salles N, Dartigues JF, Letenneur L. Detecting both current and prior Helicobacter pylori infection is important to assess its impact on dementia. Alzheimer and Dementia 2019;15(5) 721-722 (IF 17.127)
5- Albaret G, Sifré E, Floch P, Laye S, Aubert A, Dubus P, Azzi-Martin L, Giese A, Salles N, Mégraud F, Varon C, Lehours P, Roubaud-Baudron C. Alzheimer’s disease and Helicobacter pylori infection: inflammation from stomach to brain? Journal of Alzheimer’s Disease 2020;73(2):801-809. (IF 3.909).
