Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Departments of Physiology, University of Kentucky, Lexington, Kentucky, USA.
Alzheimers Dement. 2023 Jan;19(1):67-78. doi: 10.1002/alz.12639. Epub 2022 Mar 10.
Clinically, detection of disease-causing pathology associated with Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) is limited to magnetic resonance imaging and positron emission tomography scans, which are expensive and not widely accessible. Here, we assess angiogenic, inflammatory, and AD-related plasma biomarkers to determine their relationships with human post mortem neuropathology.
Plasma samples were analyzed using a digital immunoassay and pathological evaluation was performed by University of Kentucky Alzheimer's Disease Research Center neuropathologists. The association of plasma markers with neuropathology was estimated via proportional odds and logistic regressions adjusted for age.
Included cases (N = 90) showed increased tau/amyloid beta (Aβ)42 ratio, glial fibrillary acidic protein (GFAP), vascular endothelial growth factor A (VEGF-A), and placental growth factor (PlGF) were positively associated with higher level of AD neuropathological change, while higher Aβ42/Aβ40 ratio was inversely associated. Higher PlGF, VEGF-A, and interleukin 6 were inversely associated with chronic cerebrovascular disease, while Aβ42/Aβ40 ratio was positively associated.
Our results provide support for the continued study of plasma biomarkers as a clinical screening tool for AD and VCID pathology.
临床上,与阿尔茨海默病(AD)相关的致病病理学以及与认知障碍和痴呆症相关的血管因素(VCID)的检测仅限于磁共振成像和正电子发射断层扫描,这些方法昂贵且无法广泛应用。在这里,我们评估了血管生成、炎症和与 AD 相关的血浆生物标志物,以确定它们与人体死后神经病理学的关系。
使用数字免疫测定法分析血浆样本,并由肯塔基大学阿尔茨海默病研究中心的神经病理学家进行病理学评估。通过比例优势和逻辑回归,调整年龄因素,估计了血浆标志物与神经病理学之间的关联。
纳入的病例(N=90)显示,tau/淀粉样蛋白β(Aβ)42 比值升高,神经胶质纤维酸性蛋白(GFAP)、血管内皮生长因子 A(VEGF-A)和胎盘生长因子(PlGF)水平与 AD 神经病理学变化的严重程度呈正相关,而 Aβ42/Aβ40 比值则呈负相关。较高的 PlGF、VEGF-A 和白细胞介素 6 与慢性脑血管疾病呈负相关,而 Aβ42/Aβ40 比值则呈正相关。
我们的研究结果支持进一步研究血浆生物标志物作为 AD 和 VCID 病理的临床筛查工具。