Bolen MacKenzie L, Menees Kelly B, Gearing Marla, Gong Jingjing, Ren Yuqi, Merchak Andrea R, Murray Melissa E, McEachin Zachary T, Tansey Malú Gámez
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL USA.
Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL USA.
NPJ Dement. 2025;1(1):10. doi: 10.1038/s44400-025-00010-6. Epub 2025 Jun 3.
Frontotemporal lobar degeneration (FTLD) is the leading cause of dementia in patients under the age of 65. Even in a single anatomical region, there is variance within pathological protein deposition within the FTLD spectrum, which drives difficulty in post-mortem clinicopathological diagnoses. We spatially multiplexed the proteome geography at two levels of the cortex and the subcortical white matter in patients with various types of dementia (Alzheimer's disease, C9orf72, MAPT also referred to as FTLD-tau, FTLD-TDP, FTLD-GRN; = 6 per syndrome) and neurologically healthy controls (NHC). Layers II-V of the cortex from diseased individuals displayed the greatest protein dysregulation as compared to NHC. Traditional biomarkers of dementia, like phosphorylated tau proteins and Aβ42 displayed dysregulation, however, our data suggest spatial enrichment distinct to cortical sublayers. In conclusion, the specific localization of these protein deposits could be used to elucidate region-specific pathologic biomarkers unique to individual variants of dementia.
额颞叶变性（FTLD）是65岁以下患者痴呆症的主要病因。即使在单个解剖区域，FTLD谱系中的病理性蛋白质沉积也存在差异，这使得死后临床病理诊断变得困难。我们对患有各种类型痴呆症（阿尔茨海默病、C9orf72、MAPT，也称为FTLD- tau、FTLD- TDP、FTLD- GRN；每种综合征6例）的患者以及神经健康对照（NHC）的皮质和皮质下白质两个层面的蛋白质组图谱进行了空间多重分析。与NHC相比，患病个体皮质的II - V层显示出最大的蛋白质失调。痴呆症的传统生物标志物，如磷酸化tau蛋白和Aβ42表现出失调，然而，我们的数据表明在皮质亚层存在空间富集现象。总之，这些蛋白质沉积物的特定定位可用于阐明痴呆症个体变体特有的区域特异性病理生物标志物。
