Plasma biomarkers of neurodegeneration in mild cognitive impairment with Lewy bodies.
Plasma biomarkers of neurodegeneration in mild cognitive impairment with Lewy bodies.
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DOI：
10.1017/s0033291723001952
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发表时间：
2023-12
影响因子：
6.9
通讯作者：
Thomas, Alan
中科院分区：
文献类型：
--
作者：
Hamilton, Calum Alexander;O'Brien, John;Heslegrave, Amanda;Laban, Rhiannon;Donaghy, Paul;Durcan, Rory;Lawley, Sarah;Barnett, Nicola;Roberts, Gemma;Firbank, Michael;Taylor, John-Paul;Zetterberg, Henrik;Thomas, Alan
关键词：
阿尔茨海默病(AD)的血液生物标志物可以早期发现AD所致的轻度认知损害(MCI-AD)的病理改变，并可作为MCI合并路易小体(MCI-LB)的共同病理。然而，并不是所有的MCI-LB病例都以AD病理为特征。因此，神经退变的疾病通用生物标记物，如胶质纤维酸性蛋白(GFAP)或神经丝光(NFL)，可能为AD生物标记物提供有用的补充。我们的目的是比较血浆Aβ42/40、p-tau181、GFAP和NFL在区分认知健康的老年人和彼此之间的相对效用。对172名受试者(31名健康对照组，48名轻度认知功能障碍患者，28名可能患有轻度认知功能障碍，65名可能患有轻度认知功能障碍)和55名在≥1年后重复提供样本的受试者进行了血浆样本分析。样本用SIMOA4-plex分析Aβ42、Aβ40、GFAP和NFL，并纳入先前从同一队列收集的p-tau181。与对照组相比，MCI-LB可能有升高GFAP(p<；0.001)和NFL(p=0.012)的作用，但不显著降低Aβ42/40(p=0.012)。MCI-AD组GFAP和p-tau181高于MCI-LB组。GFAP能区分所有MCI亚组和对照组(AUC为0.75)，但没有血浆标志物能有效区分MCI-AD和MCI-Lb。NFL与疾病严重程度相关，并随时间的推移而增加(p=0.011)。阿尔茨海默病和星形细胞增多症/神经退行性变的标志物在MCI-LB中升高。GFAP在区分整体MCI及其亚组与健康对照组方面提供了与p-tau181类似的实用价值。
Blood biomarkers of Alzheimer's disease (AD) may allow for the early detection of AD pathology in mild cognitive impairment (MCI) due to AD (MCI-AD) and as a co-pathology in MCI with Lewy bodies (MCI-LB). However not all cases of MCI-LB will feature AD pathology. Disease-general biomarkers of neurodegeneration, such as glial fibrillary acidic protein (GFAP) or neurofilament light (NfL), may therefore provide a useful supplement to AD biomarkers. We aimed to compare the relative utility of plasma Aβ42/40, p-tau181, GFAP and NfL in differentiating MCI-AD and MCI-LB from cognitively healthy older adults, and from one another. Plasma samples were analysed for 172 participants (31 healthy controls, 48 MCI-AD, 28 possible MCI-LB and 65 probable MCI-LB) at baseline, and a subset (n = 55) who provided repeated samples after ≥1 year. Samples were analysed with a Simoa 4-plex assay for Aβ42, Aβ40, GFAP and NfL, and incorporated previously-collected p-tau181 from this same cohort. Probable MCI-LB had elevated GFAP (p < 0.001) and NfL (p = 0.012) relative to controls, but not significantly lower Aβ42/40 (p = 0.06). GFAP and p-tau181 were higher in MCI-AD than MCI-LB. GFAP discriminated all MCI subgroups, from controls (AUC of 0.75), but no plasma-based marker effectively differentiated MCI-AD from MCI-LB. NfL correlated with disease severity and increased with MCI progression over time (p = 0.011). Markers of AD and astrocytosis/neurodegeneration are elevated in MCI-LB. GFAP offered similar utility to p-tau181 in distinguishing MCI overall, and its subgroups, from healthy controls.