Macquarie Medical School, Macquarie University, North Ryde, New South Wales, Australia.
School of Medical Sciences, Edith Cowan University, Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia.
Alzheimers Dement. 2023 Jul;19(7):2790-2804. doi: 10.1002/alz.12879. Epub 2022 Dec 28.
Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility.
We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease.
Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (Aβ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished Aβ-positive from Aβ-negative ADAD participants and showed a stronger relationship with Aβ load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP.
Our findings support a role for plasma GFAP as a clinical biomarker of Aβ-related astrocyte reactivity that is associated with cognitive decline and neurodegeneration.
Plasma glial fibrillary acidic protein (GFAP) elevations appear a decade before expected symptom onset in autosomal dominant Alzheimer's disease (ADAD). Plasma GFAP was associated to amyloid positivity in asymptomatic ADAD. Plasma GFAP increased with clinical severity and predicted disease progression. Plasma and serum GFAP carried similar information in ADAD, while cerebrospinal fluid GFAP did not.
胶质纤维酸性蛋白（GFAP）是一种很有前途的阿尔茨海默病（AD）诊断和预后的基于血液的生物标志物。它与疾病相关的变化的时间、其临床相关性以及生物流体类型的依赖性将影响其临床应用。
我们评估了常染色体显性 AD（ADAD）家族的血浆、血清和脑脊液（CSF）中的 GFAP，利用可预测的发病年龄来确定疾病阶段的变化。
在淀粉样蛋白（Aβ）积累和神经退行性变及认知能力下降之前，ADAD 患者的血浆 GFAP 水平在预期症状出现前十年就出现升高。血浆 GFAP 可以区分 Aβ 阳性和 Aβ 阴性的 ADAD 患者，与无症状 ADAD 患者的 Aβ 负荷相关性更强。较高的血浆 GFAP 与神经退行性变和认知障碍的程度和速度有关。血清 GFAP 也表现出类似的关系，但 CSF GFAP 的关系不太明显。
我们的研究结果支持血浆 GFAP 作为一种与认知能力下降和神经退行性变相关的 Aβ 相关星形胶质细胞反应的临床生物标志物的作用。
在常染色体显性 AD（ADAD）中，血浆神经胶质纤维酸性蛋白（GFAP）的升高在预期症状出现前 10 年出现。在无症状 ADAD 中，血浆 GFAP 与淀粉样蛋白阳性相关。血浆 GFAP 随着临床严重程度的增加而增加，并预测疾病进展。血浆和血清 GFAP 在 ADAD 中携带相似的信息，而脑脊液 GFAP 则不然。
