脑淀粉样血管病疾病修饰治疗研究进展

doi:10.11817/j.issn.1673-9248.2024.04.014

脑淀粉样血管病（CAA）的机制尚未完全阐明，β淀粉样蛋白（Aβ）的产生-清除平衡失调引起Aβ沉积及其后续的氧化应激、炎症反应是血管壁破坏的关键环节。目前对CAA的治疗集中于出血事件的防治、对症治疗，而关于防止疾病进展的疾病修饰治疗尚无实质性成果。基于CAA可能的发病机制，前期已发现多个有望改善预后及临床结局的治疗靶点，包括减少Aβ产生、免疫介导的Aβ清除、增加Aβ生理性清除、抗氧化及抗炎等，部分靶点已有临床研究证据支撑，大部分研究仍处于临床前阶段，今后对CAA疾病修饰治疗的进一步基础和临床研究具有重要的临床意义。

关键词: 脑淀粉样血管病, 疾病修饰治疗, β淀粉样蛋白, 机制

The mechanism of cerebral amyloid angiopathy (CAA) has not been fully elucidated. The imbalance between the production and clearance of amyloid β (Aβ) leads to the deposition of Aβ and subsequent oxidative stress and inflammatory responses, which are key factors in the destruction of the vascular wall. Current treatments for CAA focus on the preventing and providing symptomatic treatment of hemorrhages while there has been no substantial progress in disease-modifying therapies to prevent disease progression. Based on the possible pathogenesis of CAA, several potential therapeutic targets have been identified that could improve prognosis and clinical outcomes, including reducing Aβ production, immune-mediated Aβ clearance, increasing physiological Aβ clearance, and anti-oxidation and anti-inflammatory measures. Some targets are supported by clinical research evidence, while most research remains still in the preclinical stage. Further basic and clinical research on disease-modifying therapies for CAA is of significant clinical importance.

Key words: Cerebral amyloid angiopathy, Disease-modifying therapy, Amyloid β, Mechanism

1	Walker L, Simpson H, Thomas AJ, et al. Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer's disease [J]. Acta Neuropathol Commun, 2024, 12(1): 28.
2	Saito S, Ihara M. New therapeutic approaches for alzheimer's disease and cerebral amyloid angiopathy [J]. Front Aging Neurosci, 2014, 6: 290.
3	吴娟娟, 倪俊. 脑淀粉样血管病发病机制的研究进展 [J]. 中国卒中杂志, 2021, 16(12): 1278-1283.
4	Gireud-Goss M, Mack AF, McCullough LD, et al. Cerebral amyloid angiopathy and blood-brain barrier dysfunction [J]. Neuroscientist, 2021, 27(6): 668-684.
5	Egan MF, Kost J, Voss T, et al. Randomized trial of verubecestat for prodromal Alzheimer's disease [J]. New Engl J Med, 2019, 380(15): 1408-1420.
6	Novak G, Streffer JR, Timmers M, et al. Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study [J]. Alzheimers Res Ther, 2020, 12(1): 58.
7	Wessels AM, Lines C, Stern RA, et al. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease [J]. Alzheimers Dement, 2020, 16(11): 1483-1492.
8	Lo AC, Evans CD, Mancini M, et al. Phase Ⅱ (NAVIGATE-AD study) results of LY3202626 effects on patients with mild Alzheimer's disease dementia [J]. J Alzheimers Dis Rep, 2021, 5(1): 321-336.
9	Schelle J, Wegenast-Braun BM, Fritschi SK, et al. Early Aβ reduction prevents progression of cerebral amyloid angiopathy [J]. Ann Neurol, 2019, 86(4): 561-571.
10	Mori T, Rezai-Zadeh K, Koyama N, et al. Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice [J]. J Biol Chem, 2012, 287(9): 6912-6927.
11	Doody RS, Raman R, Farlow M, et al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease [J]. New Engl J Med, 2013, 369(4): 341-350.
12	Coric V, Salloway S, van Dyck CH, et al. Targeting prodromal Alzheimer disease with avagacestat: a randomized clinical trial [J]. JAMA Neurol, 2015, 72(11): 1324-1333.
13	Green RC, Schneider LS, Amato DA, et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild alzheimer disease: a randomized controlled trial [J]. JAMA, 2009, 302(23): 2557-2564.
14	Salloway S, Sperling R, Keren R, et al. A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease [J]. Neurology, 2011, 77(13): 1253-1262.
15	Panza F, Lozupone M, Seripa D, et al. Amyloid-β immunotherapy for Alzheimer disease: is it now a long shot? [J]. Ann Neurol, 2019, 85(3): 303-315.
16	Zhou G, Xiang T, Xu Y, et al. Fruquintinib/ HMPL-013 ameliorates cognitive impairments and pathology in a mouse model of cerebral amyloid angiopathy (CAA) [J]. Eur J Pharmacol, 2023, 939: 175446.
17	Koudriavtseva T, Lorenzano S, Anelli V, et al. Case report: probable cerebral amyloid angiopathy-related inflammation during bevacizumab treatment for metastatic cervical cancer [J]. Front Oncol, 2021, 11: 669753.
18	Daoutsali E, Hailu TT, Buijsen RAM, et al. Antisense oligonucleotide-induced amyloid precursor protein splicing modulation as a therapeutic approach for Dutch-type cerebral amyloid angiopathy [J]. Nucleic Acid Ther, 2021, 31(5): 351-363.
19	Orgogozo JM, Gilman S, Dartigues JF, et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization [J]. Neurology, 2003, 61(1): 46-54.
20	Yadollahikhales G, Rojas JC. Anti-amyloid immunotherapies for Alzheimer's disease: a 2023 clinical update [J]. Neurotherapeutics, 2023, 20(4): 914-931.
21	Nicoll JAR, Buckland GR, Harrison CH, et al. Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer's disease [J]. Brain, 2019, 142(7): 2113-2126.
22	Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, et al. Cerebral amyloid angiopathy and Alzheimer disease-one peptide, two pathways [J]. Nat Rev Neurol, 2020, 16(1): 30-42.
23	Sperling RA, Jack CRJr, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup [J]. Alzheimers Dement, 2011, 7(4): 367-385.
24	Wisniewski T. AD vaccines: conclusions and future directions [J]. CNS Neurol Disord Drug Targets, 2009, 8(2): 160-166.
25	Wilcock DM, Jantzen PT, Li Q, et al. Amyloid-beta vaccination, but not nitro-nonsteroidal anti-inflammatory drug treatment, increases vascular amyloid and microhemorrhage while both reduce parenchymal amyloid [J]. Neuroscience, 2007, 144(3): 950-960.
26	Tanaka M, Saito S, Inoue T, et al. Potential therapeutic approaches for cerebral amyloid angiopathy and Alzheimer's disease [J]. Int J Mol Sci, 2020, 21(6): 1992.
27	Bales KR, O'Neill SM, Pozdnyakov N, et al. Passive immunotherapy targeting amyloid-β reduces cerebral amyloid angiopathy and improves vascular reactivity [J]. Brain, 2016, 139(Pt 2): 563-577.
28	Leurent C, Goodman JA, Zhang Y, et al. Immunotherapy with ponezumab for probable cerebral amyloid angiopathy [J]. Ann Clin Transl Neurol, 2019, 6(4): 795-806.
29	Sims JR, Zimmer JA, Evans CD, et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial [J]. Jama, 2023, 330(6): 512-527.
30	Greenberg SM, Cordonnier C, Schneider JA, et al. Off-label use of aducanumab for cerebral amyloid angiopathy [J]. Lancet Neurol, 2021, 20(8): 596-597.
31	Sveikata L, Charidimou A, Viswanathan A. Vessels sing their ARIAs: the role of vascular amyloid in the age of aducanumab [J]. Stroke, 2022, 53(1): 298-302.
32	Xiong M, Jiang H, Serrano JR, et al. APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function [J]. Sci Transl Med, 2021, 13(581): eabd7522.
33	Greenberg SM, Rosand J, Schneider AT, et al. A phase 2 study of tramiprosate for cerebral amyloid angiopathy [J]. Alzheimer Dis Assoc Disord, 2006, 20(4): 269-274.
34	Qi XM, Ma JF. The role of amyloid beta clearance in cerebral amyloid angiopathy: more potential therapeutic targets [J]. Transl Neurodegener, 2017, 6: 22.
35	Cozza M, Amadori L, Boccardi V. Exploring cerebral amyloid angiopathy: insights into pathogenesis, diagnosis, and treatment [J]. J Neurol Sci, 2023, 454: 120866.
36	Carpentier M, Robitaille Y, DesGroseillers L, et al. Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy [J]. J Neuropathol Exp Neurol, 2002, 61(10): 849-856.
37	Farris W, Schütz SG, Cirrito JR, et al. Loss of neprilysin function promotes amyloid plaque formation and causes cerebral amyloid angiopathy [J]. Am J Pathol, 2007, 171(1): 241-251.
38	Burrell M, Henderson SJ, Ravnefjord A, et al. Neprilysin inhibits coagulation through proteolytic inactivation of fibrinogen [J]. PLoS One, 2016, 11(7): e0158114.
39	Miners JS, Kehoe P, Love S. Neprilysin protects against cerebral amyloid angiopathy and Aβ-induced degeneration of cerebrovascular smooth muscle cells [J]. Brain Pathol, 2011, 21(5): 594-605.
40	Marr RA, Hafez DM. Amyloid-beta and Alzheimer's disease: the role of neprilysin-2 in amyloid-beta clearance [J]. Front Aging Neurosci, 2014, 6: 187.
41	Inoue Y, Ueda M, Masuda T, et al. Memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, attenuates cerebral amyloid angiopathy by increasing insulin-degrading enzyme expression [J]. Mol Neurobiol, 2019, 56(12): 8573-8588.
42	Inoue Y, Masuda T, Misumi Y, et al. Metformin attenuates vascular pathology by increasing expression of insulin-degrading enzyme in a mixed model of cerebral amyloid angiopathy and type 2 diabetes mellitus [J]. Neurosci Lett, 2021, 762: 136136.
43	Nizari S, Wells JA, Carare RO, et al. Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice [J]. Acta Neuropathol Commun, 2021, 9(1): 12.
44	Begum N, Shen W, Manganiello V. Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: Implications in cardiovascular diseases and infertility [J]. Curr Opin Pharm, 2011, 11(6): 725-729.
45	Yakushiji Y, Kawamoto K, Uchihashi K, et al. Low-dose phosphodiesterase Ⅲ inhibitor reduces the vascular amyloid burden in amyloid-β protein precursor transgenic mice [J]. Int J Mol Sci, 2020, 21(7): 2295.
46	Huang Y, Cheng Y, Wu J, et al. Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study [J]. Lancet Neurol, 2008, 7(6): 494-499.
47	Gotoh F, Tohgi H, Hirai S, et al. Cilostazol stroke prevention study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction [J]. J Stroke Cerebrovasc Dis, 2000, 9(4): 147-157.
48	Polis B, Gurevich V, Assa M, et al. Norvaline restores the BBB integrity in a mouse model of Alzheimer's disease [J]. Int J Mol Sci, 2019, 20(18): 4616.
49	Garcia-Alloza M, Prada C, Lattarulo C, et al. Matrix metalloproteinase inhibition reduces oxidative stress associated with cerebral amyloid angiopathy in vivo in transgenic mice [J]. J Neurochem, 2009, 109(6): 1636-1647.
50	Zhang YL, Wang J, Zhang ZN, et al. The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer's disease [J]. Neural Regen Res, 2022, 17(11): 2355-2363.
51	De Silva TM, Miller AA. Cerebral small vessel disease: targeting oxidative stress as a novel therapeutic strategy? [J]. Front Pharmacol, 2016, 7: 61.
52	Hamel E, Nicolakakis N, Aboulkassim T, et al. Oxidative stress and cerebrovascular dysfunction in mouse models of Alzheimer's disease [J]. Exp Physiol, 2008, 93(1): 116-120.
53	Saito S, Tanaka M, Satoh-Asahara N, et al. Taxifolin: a potential therapeutic agent for cerebral amyloid angiopathy [J]. Front Pharmacol, 2021, 12: 643357.
54	Tanaka M, Saito S, Inoue T, et al. Novel therapeutic potentials of taxifolin for amyloid-β-associated neurodegenerative diseases and other diseases: recent advances and future perspectives [J]. Int J Mol Sci, 2019, 20(9): 2139.
55	Inoue T, Saito S, Tanaka M, et al. Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy [J]. Proc Natl Acad Sci U S A, 2019, 116(20): 10031-10038.
56	Saito S, Yamamoto Y, Maki T, et al. Taxifolin inhibits amyloid-β oligomer formation and fully restores vascular integrity and memory in cerebral amyloid angiopathy [J]. J Neurol Sci, 2017, 381: 988.
57	Yan P, Zhu A, Liao F, et al. Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid angiopathy [J]. Stroke, 2015, 46(6): 1633-1640.
58	Fan R, Xu F, Previti ML, et al. Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid [J]. J Neurosci, 2007, 27(12): 3057-3063.
59	Bax F, Warren A, Fouks AA, et al. Minocycline in severe cerebral amyloid angiopathy: a single-center cohort study [J]. J Am Heart Assoc, 2024, 13(4): e033464.
60	Voigt S, Koemans EA, Rasing I, et al. Minocycline for sporadic and hereditary cerebral amyloid angiopathy (batman): study protocol for a placebo-controlled randomized double-blind trial [J]. Trials, 2023, 24(1): 378.
61	Zhou G, Ye Q, Xu Y, et al. Mitochondrial calcium uptake 3 mitigates cerebral amyloid angiopathy-related neuronal death and glial inflammation by reducing mitochondrial dysfunction [J]. Int Immunopharmacol, 2023, 117: 109614.
62	Ambi A, Stanisavljevic A, Victor TW, et al. Evaluation of copper chelation therapy in a transgenic rat model of cerebral amyloid angiopathy [J]. ACS Chem Neurosci, 2023, 14(3): 378-388.
63	Zhu X, Victor TW, Ambi A, et al. Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques [J]. Metallomics, 2020, 12(4): 539-546.
64	Han BH, Zhou ML, Johnson AW, et al. Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice [J]. Proc Natl Acad Sci U S A, 2015, 112(8): E881-890.
65	Hur J, Mateo V, Amalric N, et al. Cerebrovascular β-amyloid deposition and associated microhemorrhages in a Tg2576 alzheimer mouse model are reduced with a DHA-enriched diet [J]. FASEB J, 2018, 32(9): 4972-4983.
66	Hu M, Li T, Ma X, et al. Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model [J]. Nat Commun, 2023, 14(1): 3945.
67	Ioannou M, Fella E, Papacharalambous R, et al. Treatment of the CRND8 mouse model for cerebral amyloid angiopathy, exhibited increased levels of neuron specific enolase in brain tissue following long-term treatment with a modified C5a receptor agonist, accompanied by improved cognitive function [J]. Biochem Biophys Res Commun, 2023, 675: 78-84.
68	Boese AC, Hamblin MH, Lee JP. Neural stem cell therapy for neurovascular injury in Alzheimer's disease [J]. Exp Neurol, 2020, 324: 113112.
69	Nikolic WV, Hou H, Town T, et al. Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular beta-amyloid deposits in Alzheimer mice [J]. Stem Cells Dev, 2008, 17(3): 423-439.
70	Harach T, Jammes F, Muller C, et al. Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease [J]. Neurobiol Aging, 2017, 51: 83-96.
71	Chakraborty A, Kamermans A, van Het Hof B, et al. Angiopoietin like-4 as a novel vascular mediator in capillary cerebral amyloid angiopathy [J]. Brain, 2018, 141(12): 3377-3388.
72	March ME, Gutierrez-Uzquiza A, Snorradottir AO, et al. NAC blocks cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients [J]. Nat Commun, 2021, 12(1): 1827.
73	Li N, Zhang X, Gu Z, et al. Young plasma attenuates cognitive impairment and the cortical hemorrhage area in cerebral amyloid angiopathy model mice [J]. Ann Transl Med, 2021, 9(2): 147.
74	Qi XM, Wang C, Chu XK, et al. Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer's disease [J]. BMC Neurosci, 2018, 19(1): 2.
75	Yang J, Kou J, Lalonde R, et al. Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer's disease [J]. Brain Behav Immun, 2017, 65: 262-273.
76	Wilhelmus MM, de Jager M, Drukarch B. Tissue transglutaminase: a novel therapeutic target in cerebral amyloid angiopathy [J]. Neurodegener Dis, 2012, 10(1-4): 317-319.
77	Lifshitz V, Weiss R, Benromano T, et al. Immunotherapy of cerebrovascular amyloidosis in a transgenic mouse model [J]. Neurobiol Aging, 2012, 33(2): 432.e431-432.e413.
78	Lewis TL, Cao D, Lu H, et al. Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer disease [J]. J Biol Chem, 2010, 285(47): 36958-36968.
79	Saviano A, Casillo GM, Raucci F, et al. Supplementation with ribonucleotide-based ingredient (Ribodiet®) lessens oxidative stress, brain inflammation, and amyloid pathology in a murine model of Alzheimer [J]. Biomed Pharmacother, 2021, 139: 111579.
80	Thakker DR, Weatherspoon MR, Harrison J, et al. Intracerebroventricular amyloid-beta antibodies reduce cerebral amyloid angiopathy and associated micro-hemorrhages in aged Tg2576 mice [J]. Proc Natl Acad Sci U S A, 2009, 106(11): 4501-4506.
81	Mehla J, Singh I, Diwan D, et al. STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks [J]. Acta Neuropathol Commun, 2021, 9(1): 193.
82	Gregory JL, Prada CM, Fine SJ, et al. Reducing available soluble β-amyloid prevents progression of cerebral amyloid angiopathy in transgenic mice [J]. J Neuropathol Exp Neurol, 2012, 71(11): 1009-1017.

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Research progress in the disease-modifing therapy of cerebral amyloid angiopathy

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Research progress in the disease-modifing therapy of cerebral amyloid angiopathy