Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, Georgia, USA.
Georgetown University, School of Medicine, Washington, District of Columbia, USA.
Alzheimers Dement. 2024 Feb;20(2):1175-1189. doi: 10.1002/alz.13457. Epub 2023 Nov 6.
There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.
Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.
CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.
Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.
Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.
在高风险、多样化的人群中，确定阿尔茨海默病（AD）发展的临床前病理生理机制仍然是当务之急。我们探讨了血管损伤和神经炎症的脑脊液（CSF）标志物与中年黑人和非西班牙裔白种人（B/AA 和 NHW）参与者 AD 生物标志物之间的关系。
招募了有 AD 家族史的成年人（45-65 岁）（n=82）。在基线和第 2 年收集 CSF 和血液生物标志物。
与基线相比，CSF 总 tau（t-tau）、磷酸化 tau（p-tau）和淀粉样蛋白β（Aβ）40 在第 2 年升高。CSF 可溶性血小板衍生生长因子受体β（sPDGFRβ）水平，一种周细胞损伤的标志物，与 t-tau、p-tau、血管损伤标志物和基线及第 2 年的细胞因子呈正相关。CSF sPDGFRβ 和 tau 在 B/AA 中明显低于 NHW。
血管功能障碍和神经炎症可能先于认知能力下降和疾病病理学，在 AD 的极早期临床前阶段，并且这些关系存在种族差异。
在高风险的中年成年人中，脑脊液（CSF）阿尔茨海默病（AD）生物标志物在 2 年内发生变化。血管功能障碍的标志物与 CSF 生物标志物淀粉样蛋白β和 tau 相关。与非西班牙裔白人相比，黑人的 AD 生物标志物较低。黑人的血管功能障碍标志物较低。
