Pollaci Giuliana, Potenza Antonella, Gorla Gemma, Carrozzini Tatiana, Marinoni Giulia, De Toma Carolina, Canavero Isabella, Rifino Nicola, Boncoraglio Giorgio B, Difrancesco Jacopo C, Damavandi Payam Tabaee, Stanziano Mario, Erbetta Alessandra, Caroppo Paola, Di Fede Giuseppe, Catania Marcella, Zulueta Aida, Parati Eugenio Agostino, Bersano Anna, Gatti Laura, Storti Benedetta
From the Cerebrovascular Unit (G.P., A.P., G.G., T.C., G.M., C.T., I.C., N.R., G.B.B., A.B., L.G., B.S.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; Department of Pharmacological and Biomolecular Sciences (G.P., A.P.), University of Milan; Department of Neurology (J.C.D., P.T.D.), Fondazione IRCCS San Gerardo dei Tintori, Monza; Neuroradiology Unit (M.S., A.E.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; ALS Centre (M.S.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin; Neuropathology Unit (P.C., G.D.F., M.C.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan; and Istituti Clinici Scientifici Maugeri IRCCS (A.Z., E.A.P.), Neurorehabilitation Unit of Milan Institute, Italy.
Neurology. 2024 Oct 22;103(8):e209828. doi: 10.1212/WNL.0000000000209828. Epub 2024 Sep 16.
Recently, a subset of patients affected by cerebral amyloid angiopathy (CAA) distinguished by atypical juvenile onset and a hypothesized iatrogenic origin (iatrogenic CAA, iCAA) has emerged. β-Amyloid (Aβ) accumulation evidenced by amyloid PET positivity or CSF Aβ decrease was included in the iCAA diagnostic criteria. Conversely, diagnostic criteria for sporadic CAA (sCAA) do not involve biomarker analysis. The aim of this study was to assess CSF and plasma levels of Aβ and tau in iCAA and sCAA cohorts.
Patients affected by probable or possible CAA according to established criteria (Boston 2.0) were prospectively recruited at Fondazione IRCCS Carlo Besta and San Gerardo dei Tintori from May 2021 to January 2024. Patients with probable and possible iCAA or sCAA with available plasma and/or CSF samples were included. Clinical and neurologic data were collected, and levels of Aβ40, Aβ42, total tau, and phospho-tau (p-tau) were assessed in CSF and plasma by SiMoA and Lumipulse.
21 patients with iCAA (72% male, mean age at symptom onset 50 years [36-74]) and 32 patients with sCAA (44% male, mean age at symptom onset 68 years [52-80]) were identified. Cognitive impairment and cardiovascular risk factors in the sCAA cohort were more common compared with the iCAA cohort. Patients with sCAA and iCAA showed similar CSF levels for Aβ40 ( = 0.5 [sCAA, 95% CI 2,604-4,228; iCAA, 95% CI 1,958-3,736]), Aβ42 ( = 0.7 [sCAA, 95% CI 88-157; iCAA, 95% CI 83-155]), and total tau ( = 0.08 [sCAA, 95% CI 80-134; iCAA, 95% CI 37-99]). Plasma levels of Aβ40 ( = 0.08, 95% CI 181-222), Aβ42 ( = 0.3, 95% CI 6-8), and total tau ( = 0.4, 95% CI 3-6) were not statistically different in patients with sCAA compared with iCAA ones (Aβ40, 95% CI 153-193; Aβ42, 95% CI 6-7 and total tau, 95% CI 2-4).
Despite presenting with a younger age at onset, fewer cardiovascular risk factors, and lower cognitive impairment, patients with iCAA demonstrated Aβ and tau levels comparable with elderly patients with sCAA, supporting a common molecular paradigm between the 2 CAA forms.
最近，出现了一部分以非典型青少年发病和假定的医源性起源（医源性CAA，iCAA）为特征的脑淀粉样血管病（CAA）患者。淀粉样PET阳性或脑脊液Aβ降低所证实的β-淀粉样蛋白（Aβ）积聚被纳入iCAA诊断标准。相反，散发性CAA（sCAA）的诊断标准不涉及生物标志物分析。本研究的目的是评估iCAA和sCAA队列中脑脊液和血浆中Aβ和tau的水平。
2021年5月至2024年1月，在卡罗·贝斯塔基金会IRCCS和圣杰拉尔多·德伊·廷托里前瞻性招募了根据既定标准（波士顿2.0）可能或疑似患有CAA的患者。纳入了有可用血浆和/或脑脊液样本的可能和疑似iCAA或sCAA患者。收集临床和神经学数据，并通过SiMoA和Lumipulse评估脑脊液和血浆中Aβ40、Aβ42、总tau和磷酸化tau（p-tau）水平。
确定了21例iCAA患者（72%为男性，症状发作时平均年龄50岁[36-74岁]）和32例sCAA患者（44%为男性，症状发作时平均年龄68岁[52-80岁]）。与iCAA队列相比，sCAA队列中的认知障碍和心血管危险因素更为常见。sCAA和iCAA患者的脑脊液Aβ40（P = 0.5 [sCAA，95%CI 2,604-4,228；iCAA，95%CI 1,958-3,736]）、Aβ42（P = 0.7 [sCAA，95%CI 88-157；iCAA，95%CI 83-155]）和总tau（P = 0.08 [sCAA，95%CI 80-134；iCAA，95%CI 37-99]）水平相似。与iCAA患者相比，sCAA患者的血浆Aβ40（P = 0.08，95%CI 181-222）、Aβ42（P = 0.3，95%CI 6-8）和总tau（P = 0.4，95%CI 3-6）水平无统计学差异（Aβ40，95%CI 153-193；Aβ42，95%CI 6-7；总tau，95%CI 2-4）。
尽管iCAA患者发病年龄较轻、心血管危险因素较少且认知障碍较轻，但iCAA患者的Aβ和tau水平与老年sCAA患者相当，支持这两种CAA形式之间存在共同的分子模式。
