Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
J Neurochem. 2024 Jul;168(7):1254-1264. doi: 10.1111/jnc.16074. Epub 2024 Feb 16.
Brain amyloid-β (Aβ) deposits are key pathological hallmarks of both cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Microvascular deposits in CAA mainly consist of the Aβ peptide, whereas Aβ is the predominant variant in parenchymal plaques in AD. The relevance in pathogenesis and diagnostic accuracy of various other Aβ isoforms in CAA remain understudied. We aimed to investigate the biomarker potential of various Aβ isoforms in cerebrospinal fluid (CSF) to differentiate CAA from AD pathology. We included 25 patients with probable CAA, 50 subjects with a CSF profile indicative of AD pathology (AD-like), and 23 age- and sex-matched controls. CSF levels of Aβ, Aβ, Aβ, Aβ, Aβ, and Aβ were quantified by liquid chromatography mass spectrometry. Lower CSF levels of all six Aβ peptides were observed in CAA patients compared with controls (p = 0.0005-0.03). Except for Aβ (p = 1.0), all peptides were decreased in CAA compared with AD-like subjects (p = 0.007-0.03). Besides Aβ, none of the Aβ peptides were decreased in AD-like subjects compared with controls. All Aβ peptides combined differentiated CAA from AD-like subjects better (area under the curve [AUC] 0.84) than individual peptide levels (AUC 0.51-0.75). Without Aβ in the model (since decreased Aβ served as AD-like selection criterion), the AUC was 0.78 for distinguishing CAA from AD-like subjects. CAA patients and AD-like subjects showed distinct disease-specific CSF Aβ profiles. Peptides shorter than Aβ were decreased in CAA patients, but not AD-like subjects, which could suggest different pathological mechanisms between vascular and parenchymal Aβ accumulation. This study supports the potential use of this panel of CSF Aβ peptides to indicate presence of CAA pathology with high accuracy.
脑淀粉样蛋白-β（Aβ）沉积是脑淀粉样血管病（CAA）和阿尔茨海默病（AD）的主要病理学特征。CAA 的微血管沉积物主要由 Aβ 肽组成，而 Aβ 是 AD 实质斑块中主要的变异体。CAA 中各种其他 Aβ 同种型在发病机制和诊断准确性方面的相关性仍研究不足。我们旨在研究脑脊液（CSF）中各种 Aβ 同种型的生物标志物潜力，以区分 CAA 与 AD 病理学。我们纳入了 25 例可能的 CAA 患者、50 例具有 AD 病理学特征的 CSF 谱的受试者（AD 样）和 23 名年龄和性别匹配的对照者。通过液相色谱-质谱法定量 CSF 中 Aβ、Aβ、Aβ、Aβ、Aβ 和 Aβ 的水平。与对照组相比，CAA 患者的所有六种 Aβ 肽的 CSF 水平均较低（p = 0.0005-0.03）。除 Aβ（p = 1.0）外，与 AD 样受试者相比，所有肽在 CAA 中均减少（p = 0.007-0.03）。与对照组相比，AD 样受试者中除 Aβ 外，其他 Aβ 肽均未减少。与单独的肽水平（AUC 0.51-0.75）相比，所有 Aβ 肽的组合更好地区分了 CAA 与 AD 样受试者（AUC 0.84）。在模型中没有 Aβ（因为降低的 Aβ 是 AD 样选择标准）时，区分 CAA 与 AD 样受试者的 AUC 为 0.78。CAA 患者和 AD 样受试者表现出明显的疾病特异性 CSF Aβ 谱。在 CAA 患者中，比 Aβ 短的肽减少，但在 AD 样受试者中没有减少，这可能表明血管性和实质 Aβ 积聚之间存在不同的病理机制。这项研究支持使用该 CSF Aβ 肽组来准确指示 CAA 病理学的存在。
