| First Author | Puig KL | Year | 2015 |
| Journal | J Alzheimers Dis | Volume | 44 |
| Issue | 4 | Pages | 1263-78 |
| PubMed ID | 25408221 | Mgi Jnum | J:351354 |
| Mgi Id | MGI:7663103 | Doi | 10.3233/JAD-142259 |
| Citation | Puig KL, et al. (2015) Overexpression of mutant amyloid-beta protein precursor and presenilin 1 modulates enteric nervous system. J Alzheimers Dis 44(4):1263-78 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disorder histologically characterized by amyloid-beta (Abeta) protein accumulation and activation of associated microglia. Although these features are well described in the central nervous system, the process and consequences of Abeta accumulation in the enteric nervous system have not been extensively studied. We hypothesized that Abeta also may accumulate in the enteric nervous system and lead to immune cell activation and neuronal dysfunction in the digestive tract not unlike that observed in diseased brain. To test this hypothesis, ileums of the small intestine of thirteen month old AbetaPP/PS1 and C57BL/6 (wild type) mice were collected and analyzed using immunohistochemistry, western blot analysis, cytokine arrays, and ELISA. AbetaPP/PS1 mice demonstrated no differences in intestinal motility or water absorption but elevated luminal IgA levels compared to wild type mice. They also had increased protein levels of AbetaPP and the proteolytic enzyme, BACE, corresponding to an increase in Abeta1-40 in the intestinal lysate as well as an increase in both Abeta1-40 and Abeta1-42 in the stool. This correlated with increased protein markers of proinflammatory and immune cell activation. Histologic analysis localized AbetaPP within enteric neurons but also intestinal epithelial cells with elevated Abeta immunoreactivity in the AbetaPP/PS1 mice. The presence of AbetaPP, Abeta, and CD68 immunoreactivity in the intestines of some patients with neuropathologically-confirmed AD are consistent with the findings in this mouse model. These data support the hypothesis that in AD the intestine, much like the brain, may develop proinflammatory and immune changes related to AbetaPP and Abeta. |
