Brusini Lorenza, Dolci Giorgio, Pini Lorenzo, Cruciani Federica, Pizzagalli Fabrizio, Provero Paolo, Menegaz Gloria, Boscolo Galazzo Ilaria
Department of Engineering for Innovation Medicine, University of Verona, 37134 Verona, Italy.
Department of Computer Science, University of Verona, 37134 Verona, Italy.
Int J Mol Sci. 2024 Nov 29;25(23):12871. doi: 10.3390/ijms252312871.
Bridging the gap between cortical morphometric remodeling and gene expression can help to clarify the effects of the selective brain accumulation of Amyloid-β (Aβ) and tau proteins occurring in the Alzheimer's disease (AD). To this aim, we derived morphometric similarity (MS) networks from 126 Aβ- and tau-positive (Aβ+/tau+) and 172 Aβ-/tau- subjects, and we investigated the association between group-wise regional MS differences and transcriptional correlates thanks to an imaging transcriptomics approach grounded in the Allen Human Brain Atlas (AHBA). The expressed gene with the highest correlation with MS alterations was , a gene related to Aβ homeostasis. In addition, notably, among the most promising results derived from the enrichment analysis, we found the immune response to be a biological process and astrocytes, microglia, and oligodendrocyte precursors for the cell types. In summary, by relating cortical MS and AHBA-derived transcriptomics, we were able to retrieve findings suggesting the biological mechanisms underlying the Aβ- and tau- induced cortical MS alterations in the AD continuum.
弥合皮质形态计量重塑与基因表达之间的差距，有助于阐明阿尔茨海默病（AD）中淀粉样β（Aβ）和tau蛋白在大脑中选择性积累的影响。为此，我们从126名Aβ和tau蛋白呈阳性（Aβ+/tau+）以及172名Aβ-/tau-的受试者中得出形态计量相似性（MS）网络，并借助基于艾伦人类大脑图谱（AHBA）的成像转录组学方法，研究了组间区域MS差异与转录相关性之间的关联。与MS改变相关性最高的表达基因是 ，一个与Aβ体内平衡相关的基因。此外，值得注意的是，在富集分析得出的最有前景的结果中，我们发现免疫反应是一个生物学过程，而星形胶质细胞、小胶质细胞和少突胶质细胞前体是细胞类型。总之，通过将皮质MS与源自AHBA的转录组学联系起来，我们能够获得一些发现，这些发现提示了AD连续体中Aβ和tau诱导的皮质MS改变背后的生物学机制。
