血浆神经胶质纤维酸性蛋白与 18F-SMBT-1 PET 相关：两种潜在的阿尔茨海默病星形胶质细胞反应生物标志物。
Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.
机构信息
Macquarie Medical School, Macquarie University, North Ryde, NSW, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
出版信息
J Alzheimers Dis. 2023;92(2):615-628. doi: 10.3233/JAD-220908.
BACKGROUND
Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD.
OBJECTIVE
The objective of this study was to evaluate the association between the abovementioned astrocyte reactivity biomarkers.
METHODS
Plasma GFAP and Aβ were measured using the Simoa® platform in participants who underwent brain 18F-SMBT-1 and Aβ-PET imaging, comprising 54 healthy control (13 Aβ-PET+ and 41 Aβ-PET-), 11 mild cognitively impaired (3 Aβ-PET+ and 8 Aβ-PET-) and 6 probable AD (5 Aβ-PET+ and 1 Aβ-PET-) individuals. Linear regressions were used to assess associations of interest.
RESULTS
Plasma GFAP was associated with 18F-SMBT-1 signal in brain regions prone to early Aβ deposition in AD, such as the supramarginal gyrus (SG), posterior cingulate (PC), lateral temporal (LT) and lateral occipital cortex (LO). After adjusting for age, sex, APOE ɛ4 genotype, and soluble Aβ (plasma Aβ42/40 ratio), plasma GFAP was associated with 18F-SMBT-1 signal in the SG, PC, LT, LO, and superior parietal cortex (SP). On adjusting for age, sex, APOE ɛ4 genotype and insoluble Aβ (Aβ-PET), plasma GFAP was associated with 18F-SMBT-1 signal in the SG.
CONCLUSION
There is an association between plasma GFAP and regional 18F-SMBT-1 PET, and this association appears to be dependent on brain Aβ load.
背景
星形胶质细胞反应性是阿尔茨海默病（AD）连续体的早期事件。血浆神经胶质纤维酸性蛋白（GFAP）被认为反映了星形胶质细胞反应性，在从临床前到痴呆阶段的 AD 连续体中升高。在 AD 中使用 18F-SMBT-1 PET 观察到的反应性星形胶质细胞中，单胺氧化酶-B（MAO-B）也升高。
目的
本研究旨在评估上述星形胶质细胞反应性生物标志物之间的关联。
方法
使用 Simoa®平台测量了接受脑 18F-SMBT-1 和 Aβ-PET 成像的参与者的血浆 GFAP 和 Aβ，参与者包括 54 名健康对照者（13 名 Aβ-PET+和 41 名 Aβ-PET-），11 名轻度认知障碍者（3 名 Aβ-PET+和 8 名 Aβ-PET-）和 6 名可能的 AD 患者（5 名 Aβ-PET+和 1 名 Aβ-PET-）。线性回归用于评估感兴趣的关联。
结果
血浆 GFAP 与 AD 中易于早期 Aβ沉积的脑区（如缘上回（SG）、后扣带（PC）、外侧颞叶（LT）和外侧枕叶皮质（LO））的 18F-SMBT-1 信号相关。在调整年龄、性别、APOE ɛ4 基因型和可溶性 Aβ（血浆 Aβ42/40 比值）后，血浆 GFAP 与 SG、PC、LT、LO 和顶叶上回（SP）的 18F-SMBT-1 信号相关。在调整年龄、性别、APOE ɛ4 基因型和不溶性 Aβ（Aβ-PET）后，血浆 GFAP 与 SG 的 18F-SMBT-1 信号相关。
结论
血浆 GFAP 与区域性 18F-SMBT-1 PET 之间存在关联，这种关联似乎取决于脑内 Aβ 负荷。
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