Edwards Natalie C, Lao Patrick J, Alshikho Mohamad J, Ericsson Olivia M, Rizvi Batool, Petersen Melissa E, O'Bryant Sid, Flores-Aguilar Lisi, Simoes Sabrina, Mapstone Mark, Tudorascu Dana L, Janelidze Shorena, Hansson Oskar, Handen Benjamin L, Christian Bradley T, Lee Joseph H, Lai Florence, Rosas H Diana, Zaman Shahid, Lott Ira T, Yassa Michael A, Gutierrez José, Wilcock Donna M, Head Elizabeth, Brickman Adam M
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York City, New York, USA.
Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York City, New York, USA.
Alzheimers Dement. 2025 Oct;21(10):e70726. doi: 10.1002/alz.70726.
Despite having few vascular risk factors, people with Down syndrome (DS) have MRI evidence of cerebrovascular disease (CVD) and neuroinflammation that worsens with Alzheimer's disease (AD) severity. We investigated whether markers of CVD and inflammation are associated with AD-related diagnostic progression in people with DS.
We included 149 participants (mean age [SD] = 44.6 [9]) from the Alzheimer's Biomarkers Consortium-Down Syndrome who had two (n = 24) or three follow-up visits (n = 125). We derived white matter hyperintensity (WMH) volume and plasma biomarker (glial fibrillary acidic protein [GFAP], amyloid beta [Aβ]42/Aβ40, hyperphosphorylated tau-217 [p-tau217], and neurofilament light [NfL]) concentrations at baseline and examined their association with progression in clinical diagnosis.
Higher baseline WMH volume and higher GFAP were associated with a greater likelihood of diagnostic progression. Combining WMH and GFAP with p-tau217 improved clinical conversion classification accuracy over AD biomarkers alone. Among individuals with evidence of amyloidosis, both WMH and GFAP were associated with clinical progression.
In DS, markers of CVD and inflammation are independently and synergistically associated with clinical AD progression.
Higher baseline white matter hyperintensity (WMH) volume and plasma glial fibrillary acidic protein (GFAP) concentration were associated with a higher likelihood of progressing from cognitively stable to either mild cognitive impairment or clinical Alzheimer's disease in Down syndrome. WMH volume and GFAP concentration discriminated between those who progressed and those who did not. Models including the independent and interactive effects of WMH and GFAP more accurately discriminated between participants who progressed diagnostically from those who did not. Individuals with evidence of amyloid pathology were more likely to progress if they also had elevated WMH or GFAP.
尽管唐氏综合征（DS）患者的血管危险因素较少，但磁共振成像（MRI）显示他们存在脑血管疾病（CVD）和神经炎症，且随着阿尔茨海默病（AD）病情加重而恶化。我们研究了CVD和炎症标志物是否与DS患者AD相关的诊断进展有关。
我们纳入了来自阿尔茨海默病生物标志物联盟 - 唐氏综合征研究的149名参与者（平均年龄[标准差]=44.6[9]岁），其中24人进行了两次随访，125人进行了三次随访。我们在基线时得出白质高信号（WMH）体积和血浆生物标志物（胶质纤维酸性蛋白[GFAP]、淀粉样β蛋白[Aβ]42/Aβ40、高磷酸化tau-217[p-tau217]和神经丝轻链蛋白[NfL]）浓度，并检查它们与临床诊断进展的关联。
较高的基线WMH体积和较高的GFAP与诊断进展的可能性更大相关。将WMH和GFAP与p-tau217结合使用，比单独使用AD生物标志物能提高临床转化分类的准确性。在有淀粉样变性证据的个体中，WMH和GFAP均与临床进展相关。
在DS中，CVD和炎症标志物与临床AD进展独立且协同相关。
较高的基线白质高信号（WMH）体积和血浆胶质纤维酸性蛋白（GFAP）浓度与唐氏综合征患者从认知稳定进展为轻度认知障碍或临床阿尔茨海默病的可能性较高相关。WMH体积和GFAP浓度可区分进展者和未进展者。包含WMH和GFAP独立及交互作用的模型能更准确地区分诊断进展的参与者和未进展的参与者。有淀粉样病理证据的个体，如果同时WMH或GFAP升高，则更有可能进展。
