Palermo Francesca, Marrocco Nicole, Dacomo Letizia, Grisafi Elena, Moresi Viviana, Sanna Alessia, Massimi Lorenzo, Musella Marianna, Maugeri Laura, Bukreeva Inna, Fiordaliso Fabio, Corbelli Alessandro, Junemann Olga, Eckermann Marina, Cloetens Peter, Weitkamp Timm, Gigli Giuseppe, de Rosbo Nicole Kerlero, Balducci Claudia, Cedola Alessia
Institute of Nanotechnology - CNR, Rome, Italy.
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Sci Adv. 2025 Jan 31;11(5):eadr8511. doi: 10.1126/sciadv.adr8511.
Alzheimer's disease (AD), a debilitating neurodegenerative disorder, remains one of the foremost public health challenges affecting more than 30 million people worldwide with the etiology still largely enigmatic. The intricate gut-brain axis, serving as a vital communication network between the gut and the brain, appears to wield influence in the progression of AD. Our study showcases the remarkable precision of x-ray phase-contrast tomography (XPCT) in conducting an advanced three-dimensional examination of gut cellular composition and structure. The exploitation of micro- and nano-XPCT on various AD mouse models unveiled relevant alterations in villi and crypts, cellular transformations in Paneth and goblet cells, along with the detection of telocytes, neurons, erythrocytes, and mucus secretion by goblet cells within the gut cavity. The observed gut structural variations may elucidate the transition from dysbiosis to neurodegeneration and cognitive decline. Leveraging XPCT could prove pivotal in early detection and prognosis of the disease.
阿尔茨海默病(AD)是一种使人衰弱的神经退行性疾病,仍然是最主要的公共卫生挑战之一,全球有超过3000万人受其影响,其病因在很大程度上仍然是个谜。复杂的肠-脑轴作为肠道与大脑之间至关重要的通讯网络,似乎在AD的进展中发挥着作用。我们的研究展示了X射线相衬断层扫描(XPCT)在对肠道细胞组成和结构进行先进的三维检查方面的卓越精度。对各种AD小鼠模型进行的微米和纳米XPCT研究揭示了绒毛和隐窝的相关改变、潘氏细胞和杯状细胞的细胞变化,以及在肠腔内检测到的telocytes、神经元、红细胞和杯状细胞的粘液分泌。观察到的肠道结构变化可能有助于阐明从肠道菌群失调到神经退行性变和认知衰退的转变。利用XPCT可能对该疾病的早期检测和预后至关重要。