阿尔茨海默病与血脑屏障的相关性研究进展

doi:10.3969/j.issn.1006-5725.2024.11.023

Abstract

Abstract:

Numerous studies have confirmed that Alzheimer's disease is a disorder related to dysfunction of blood brain barrier （BBB）. How to improve the physiological function of BBB by restoring its structural integrity， and then improve the outcome and prognosis of AD will certainly bring new perspectives and opportunities for the prevention and treatment of this chronic disease. In this article， we review the research progress on AD from three aspects including the structural and functional changes of BBB and its pathogenesis， biomarkers and therapeutic targets.

Key words: Alzheimer's disease, blood-brain barrier, biomarkers, therapeutic targets

CLC Number:

R741.02

Jie SHEN,Guihua. XU. Research progress in the relationship between Alzheimer′s disease and blood⁃brain barrier[J]. The Journal of Practical Medicine, 2024, 40(11): 1602-1606.

References 42

1	王英全，梁景宏，贾瑞霞，等. 2020-2050年中国阿尔茨海默病患病情况预测研究［J］. 阿尔茨海默病及相关病， 2019，2（1）：289-298. doi:10.3969/j.issn.2096-5516.2019.01.012 doi: 10.3969/j.issn.2096-5516.2019.01.012
2	GRIFFITHS J， GRANT S G N. Synapse pathology in Alzheimer's disease［J］. Semin Cell Dev Biol. 2023，139：13-23. doi:10.1016/j.semcdb.2022.05.028 doi: 10.1016/j.semcdb.2022.05.028
3	LEE R L， FUNK K E. Imaging blood-brain barrier disruption in neuroinflammation and Alzheimer's disease［J］. Front Aging Neurosci， 2023，15：1144036. doi:10.3389/fnagi.2023.1144036 doi: 10.3389/fnagi.2023.1144036
4	NEHRA G， BAUER B， HARTZ A M S. Blood-brain barrier leakage in Alzheimer's disease： from discovery to clinical relevance［J］. Pharmacol Ther， 2022，234：108119. doi:10.1016/j.pharmthera.2022.108119 doi: 10.1016/j.pharmthera.2022.108119
5	SHEN J， XU G， ZHU R， et al. PDGFR-β restores blood-brain barrier functions in a mouse model of focal cerebral ischemia［J］. J Cereb Blood Flow Metab， 2019，39（8）：1501-1515. doi:10.1177/0271678x18769515 doi: 10.1177/0271678x18769515
6	GLENNER G G. Congophilic microangiopathy in the pathogenesis of Alzheimer's syndrome （presenile dementia）［J］. Med Hypotheses， 1979，5（11）：1231-1236. doi:10.1016/0306-9877(79)90005-7 doi: 10.1016/0306-9877(79)90005-7
7	MOON Y， LIM C， KIM Y， et al. Sex-related differences in regional blood-brain barrier integrity in non-demented elderly subjects［J］. Int J Mol Sci， 2021，22（6）：2860. doi:10.3390/ijms22062860 doi: 10.3390/ijms22062860
8	UCHIDA Y， KAN H， SAKURAI K， et al. Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias［J］. Front Aging Neurosci， 2023，15：1111448. doi:10.3389/fnagi.2023.1111448 doi: 10.3389/fnagi.2023.1111448
9	BRUNO M， BONOMI C G， RICCI F， et al. Blood-brain barrier permeability is associated with different neuroinflammatory profiles in Alzheimer's disease［J］. Eur J Neurol， 2023，31（1）：e16095. doi:10.1111/ene.16095 doi: 10.1111/ene.16095
10	MONTEIRO A R， BARBOSA D J， REMIÃO F， et al. Alzheimer's disease： Insights and new prospects in disease pathophysiology， biomarkers and disease-modifying drugs［J］. Biochem Pharmacol， 2023，211：115522. doi:10.1016/j.bcp.2023.115522 doi: 10.1016/j.bcp.2023.115522
11	ITO S， YAGI R， OGATA S， et al. Proteomic alterations in the brain and blood-brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer's disease［J］. Fluids Barriers CNS， 2023，20（1）：66. doi:10.1186/s12987-023-00466-9 doi: 10.1186/s12987-023-00466-9
12	MONTAGNE A， BARNES S R， SWEENEY M D， et al. blood-brain barrier breakdown in the aging human hippocampus［J］. Neuron， 2015，85（2）：296-302. doi:10.1016/j.neuron.2014.12.032 doi: 10.1016/j.neuron.2014.12.032
13	BUTTS B， HUANG H， HU W T， et al. sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race： The ASCEND Study［J］. Alzheimers Dement， 2023，20（2）：1175-1189. doi:10.1002/alz.13457 doi: 10.1002/alz.13457
14	TING K K， COLEMAN P， KIM H J， et al. Vascular senescence and leak are features of the early breakdown of the blood-brain barrier in Alzheimer's disease models［J］. Geroscience， 2023，45（6）：3307-3331. doi:10.1007/s11357-023-00927-x doi: 10.1007/s11357-023-00927-x
15	EISENMENGER L B， PERET A， FAMAKIN B M， et al. Vascular contributions to Alzheimer's disease［J］. Transl Res， 2023，254：41-53. doi:10.1016/j.trsl.2022.12.003 doi: 10.1016/j.trsl.2022.12.003
16	CERASUOLO M， PAPA M， COLANGELO A M， et al. Alzheimer's Disease from the amyloidogenic theory to the puzzling crossroads between vascular， metabolic and energetic maladaptive plasticity［J］. Biomedicines， 2023，11（3）：861. doi:10.3390/biomedicines11030861 doi: 10.3390/biomedicines11030861
17	SANTISTEBAN M M， IADECOLA C， CARNEVALE D. Hypertension， neurovascular dysfunction， and cognitive impairment［J］. Hypertension， 2023，80（1）：22-34. doi:10.1161/hypertensionaha.122.18085 doi: 10.1161/hypertensionaha.122.18085
18	赵红，李潇，王翠.关注少突胶质细胞：阿尔茨海默病治疗的新靶点［J］.实用医学杂志， 2023， 39（13）：1595-1599. doi:10.3969/j.issn.1006-5725.2023.13.001 doi: 10.3969/j.issn.1006-5725.2023.13.001
19	PETRUSHANKO I Y， MITKEVICH V A， MAKAROV A A. Effect of β-amyloid on blood-brain barrier properties and function［J］. Biophys Rev， 2023，15（2）：183-197. doi:10.1007/s12551-023-01052-x doi: 10.1007/s12551-023-01052-x
20	SHI H， KORONYO Y， FUCHS D T， et al. Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients［J］. Alzheimers Dement， 2023，19（11）：5185-5197. doi:10.1002/alz.13086 doi: 10.1002/alz.13086
21	CUSTODIA A， ARAMBURU-NÚÑEZ M， RODRÍGUEZ-ARRIZABALAGA M， et al. Biomarkers assessing endothelial dysfunction in Alzheimer's Disease［J］. Cells， 2023，12（6）：962. doi:10.3390/cells12060962 doi: 10.3390/cells12060962
22	ALGHANIMY A， MARTIN C， GALLAGHER L， et al. The effect of a novel AQP4 facilitator， TGN-073， on glymphatic transport captured by diffusion MRI and DCE-MRI［J］. PLoS One， 2023，18（3）：e0282955. doi:10.1371/journal.pone.0282955 doi: 10.1371/journal.pone.0282955
23	SELF W K， HOLTZMAN D M. Emerging diagnostics and therapeutics for Alzheimer disease［J］. Nat Med， 2023，29（9）：2187-2199. doi:10.1038/s41591-023-02505-2 doi: 10.1038/s41591-023-02505-2
24	MUSAEUS C S， GLEERUP H S， HASSELBALCH S G， et al. Progression of blood-brain barrier leakage in patients with Alzheimer's Disease as measured with the cerebrospinal fluid/plasma albumin ratio over time［J］. J Alzheimers Dis Rep， 2023，7（1）：535-541. doi:10.3233/adr-230016 doi: 10.3233/adr-230016
25	SCHLIEP G， FELGENHAUER K. Serum-CSF protein gradients， the blood-GSF barrier and the local immune response［J］. J Neurol， 1978，218（2）：77-96. doi:10.1007/bf02402169 doi: 10.1007/bf02402169
26	KRISHNAN P， MURPHY A， AVIV R I. CT-based techniques for brain perfusion［J］. Top Magn Reson Imaging， 2017，26（3）：113-119. doi:10.1097/rmr.0000000000000129 doi: 10.1097/rmr.0000000000000129
27	VOORTER P H M， VAN DINTHER M， JANSEN W J， et al. Blood-brain barrier disruption and perivascular spaces in small vessel disease and neurodegenerative diseases： a review on MRI methods and insights［J］. J Magn Reson Imaging， 2024，59（2）：397-411. doi:10.1002/jmri.28989 doi: 10.1002/jmri.28989
28	MONTAGNE A， NATION D A， SAGARE A P， et al. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline［J］. Nature， 2020，581（7806）：71-76. doi:10.1038/s41586-020-2247-3 doi: 10.1038/s41586-020-2247-3
29	KNOX E G， ABURTO M R， CLARKE G， et al. The blood-brain barrier in aging and neurodegeneration［J］. Mol Psychiatry， 2022，27（6）：2659-2673. doi:10.1038/s41380-022-01511-z doi: 10.1038/s41380-022-01511-z
30	HUANG P， ZHANG M. Magnetic resonance imaging studies of neurodegenerative disease： from methods to translational research［J］. Neurosci Bull， 2023，39（1）：99-112. doi:10.1007/s12264-022-00905-x doi: 10.1007/s12264-022-00905-x
31	POLIAKOVA T， LEVIN O， ARABLINSKIY A， et al. Cerebral microbleeds in early Alzheimer's disease［J］. J Neurol， 2016，263（10）：1961-1968. doi:10.1007/s00415-016-8220-2 doi: 10.1007/s00415-016-8220-2
32	VÁZQUEZ-JUSTES D， AGUIRREGOICOA I， FERNANDEZ L， et al. Clinical impact of microbleeds in patients with Alzheimer's disease［J］. BMC Geriatr， 2022，22（1）：774. doi:10.1186/s12877-022-03456-y doi: 10.1186/s12877-022-03456-y
33	SCHOEMAKER D， ZANON ZOTIN M C， CHEN K， et al. White matter hyperintensities are a prominent feature of autosomal dominant Alzheimer's disease that emerge prior to dementia［J］. Alzheimers Res Ther， 2022，14（1）：89. doi:10.1186/s13195-022-01030-7 doi: 10.1186/s13195-022-01030-7
34	BRUNDEL M， HERINGA S M， DE BRESSER J， et al. High prevalence of cerebral microbleeds at 7Tesla MRI in patients with early Alzheimer's disease［J］. J Alzheimers Dis， 2012，31（2）：259-263. doi:10.3233/jad-2012-120364 doi: 10.3233/jad-2012-120364
35	中国痴呆与认知障碍诊治指南写作组，中国医师协会神经内科医师分会认知障碍疾病专业委员会.中国阿尔茨海默病一级预防指南［J］.中华医学杂志， 2020， 100（35）：2721-2735. doi:10.3760/cma.j.cn112137-20200702-02017 doi: 10.3760/cma.j.cn112137-20200702-02017
36	PATRIZIA CAVAZZONI， FDA Center for Drug Evaluation and Research. FDA′s decision to approve new treatment for Alzheimer′s Disease［EB/OL］.（2021-06-07）［2023-04-24］. .
37	BUDD HAEBERLEIN S， AISEN P S， BARKHOF F， et al. Two randomized phase 3 studies of aducanumab in early Alzheimer's Disease［J］. J Prev Alzheimers Dis， 2022，9（2）：197-210.
38	SWANSON C J， ZHANG Y， DHADDA S， et al. A randomized， double-blind， phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab， an anti-Aβ protofibril antibody［J］. Alzheimers Res Ther， 2021，13（1）：80. doi:10.1186/s13195-022-00995-9 doi: 10.1186/s13195-022-00995-9
39	MINTUN M A， LO A C， DUGGAN EVANS C， et al. Donanemab in early Alzheimer's Disease［J］. N Engl J Med， 2021，384（18）：1691-1704. doi:10.1056/nejmoa2100708 doi: 10.1056/nejmoa2100708
40	ZHOU C， ZHANG J， LUO X， et al. Sodium oligomannate electrostatically binds to Aβ and blocks its aggregation［J］. J Phys Chem B， 2023，127（9）：1983-1994. doi:10.1021/acs.jpcb.3c00280 doi: 10.1021/acs.jpcb.3c00280
41	XIAO S， CHAN P， WANG T， et al. A 36-week multicenter， randomized， double-blind， placebo-controlled， parallel-group， phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia［J］. Alzheimers Res Ther， 2021，13（1）：62.
42	YANG A C， VEST R T， KERN F， et al. A human brain vascular atlas reveals diverse mediators of Alzheimer's risk［J］. Nature， 2022，603（7903）：885-892. doi:10.1038/s41586-021-04369-3 doi: 10.1038/s41586-021-04369-3

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Research progress in the relationship between Alzheimer′s disease and blood⁃brain barrier

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