Morphological changes in the enteric nervous system of aging and APP23 transgenic mice

Gastrointestinal motility disorders often pose a debilitating problem, especially in elderly patients. In addition, they are frequently occurring co-morbidities in dementia. Whereas a failing enteric nervous system has already been shown to be involved in gastrointestinal motility disorders and in Parkinson's disease, a relationship with the neurodegenerative process of Alzheimer's disease was not yet shown. Therefore, we sought to document quantitative changes in the distribution of βIII-tubulin (general neuronal marker), Substance P, neuronal nitric oxide synthase (NOS), glial fibrillary acidic protein (GFAP) and S-100 immunoreactivity in addition to a qualitative assessment of the presence of amyloid in the small and large intestines of 6, 12 and 18-month-old wild type and transgenic Thy-1-APP23 mice. Amyloid deposits were seen in the vasculature, the mucosal and muscle layer of both heterozygous and wild type mice. Amyloidβ1–42 could not be detected, pointing to a different amyloid composition than that found in senile plaques in the mice's brains. The finding of an increased density of βIII-tubulin-, Substance P- and NOS-IR-nerve fibres in heterozygous mice could not undoubtedly be related to amyloid deposition or to an activation of glial cells. Therefore, the alterations at the level of the enteric nervous system and the deposition of amyloid seem not primarily involved in the pathogenesis of Alzheimer's disease. At most they are secondary related to the neurodegenerative process. Additionally, our data could not show extensive neuronal or glial cell loss associated with aging, in contrast to other reports. Instead an increase in S100-IR was observed in senescent mice.

Research Highlights► Changes in enteric nervous system are not primarily involved in Alzheimer's disease. ► The density of enteric nerve fibres was increased in APP23 transgenic mice. ► Loss of enteric neurons with aging does not occur in the murine small intestine. ► Intestinal amyloidosis develops irrespective of Alzheimer's disease pathology.