Academic Journal
Intra‐gastrointestinal amyloid‐β1–42 oligomers perturb enteric function and induce Alzheimer's disease pathology
| العنوان: | Intra‐gastrointestinal amyloid‐β1–42 oligomers perturb enteric function and induce Alzheimer's disease pathology |
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| المؤلفون: | Sun, Yayi, Sommerville, Nerina R., Liu, Julia Yuen Hang, Ngan, Man Piu, Poon, Daniel, Ponomarev, Eugene D., Lu, Zengbing, Kung, Jeng S. C., Rudd, John A. |
| المصدر: | The Journal of Physiology ; volume 598, issue 19, page 4209-4223 ; ISSN 0022-3751 1469-7793 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2020 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Key points Alzheimer's disease (AD) patients and transgenic mice have beta‐amyloid (Aβ) aggregation in the gastrointestinal (GI) tract. It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion‐like properties. The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β‐amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits. These data reveal a previously undiscovered mechanism that potentially contributes to the development of AD. Abstract Alzheimer's disease (AD) is the most common age‐related cause of dementia, characterised by extracellular beta‐amyloid (Aβ) plaques and intracellular phosphorylated tau tangles in the brain. Aβ deposits have also been observed in the gastrointestinal (GI) tract of AD patients and transgenic mice, with overexpression of amyloid precursor protein. In the present studies, we investigate whether intra‐GI administration of Aβ can potentially induce amyloidosis in the central nervous system (CNS) and AD‐related pathology such as dementia. We micro‐injected Aβ1–42 oligomers (4 μg per site, five sites) or vehicle (saline, 5 μl) into the gastric wall of ICR mice under general anaesthesia. Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555‐labelled Aβ1–42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons. At 1 month, HiLyte Fluor 555‐labelled Aβ1–42 in the body of the stomach and proximal colon had partly re‐distributed to the fundus and jejunum. At 1 year, the jejunum showed functional alterations in neuromuscular coupling ( P < 0.001), and Aβ deposits were present in the vagus and brain, with animals exhibiting cognitive impairments in the Y‐maze spontaneous alteration test ( P ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1113/jp279919 |
| DOI: | 10.1113/JP279919 |
| الاتاحة: | http://dx.doi.org/10.1113/jp279919 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2FJP279919 https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP279919 https://onlinelibrary.wiley.com/doi/full-xml/10.1113/JP279919 https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP279919 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.33739C4C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1113/jp279919 |
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