[1] TAJES M，RAMOS-FERNANDEZ E，WENGJIANG

X，et al. The blood-brain barrier：structure，

function and therapeutic approaches to cross it[J].

Mol Membr Biol，2014，31（5）：152-167.

[2] HAWKINS R A，O’KANE R L，SIMPSON I A，et

al. Structure of the blood-brain barrier and its role in

the transport of amino acids[J]. J Nutr，2006，136（1

suppl）：218S-226S.

[3] CHOW B W，GU C. The molecular constituents of

the blood-brain barrier[J]. Trends Neurosci，2015，38

（10）：598-608.

[4] SWEENEY M D，AYYADURAI S，ZLOKOVIC B

V. Pericytes of the neurovascular unit：Key functions

and signaling pathways[J]. Nat Neurosci，2016，19

（6）：771-783.

[5] BELL R D，WINKLER E A，SAGARE A P，et al.

Pericytes control key neurovascular functions and

neuronal phenotype in the adult brain and during

brain aging[J]. Neuron，2010，68（3）：409-427.

[6] HAYDON P G，CARMIGNOTO G. Astrocyte

control of synaptic transmission and neurovascular

coupling[J]. Physiol Rev，2006，86（3）：1009-1031.

[7] BALLABH P，BRAUN A，NEDERGAARD M.

The blood-brain barrier：an overview Structure，

regulation，and clinical implications[J]. Neurobiol

Dis，2004，16（1）：1-13.

[8] 赵海君，钱易，崔毓桂，等. 紧密连接的结构与功

能[J]. 国际生殖健康/计划生育杂志，2013，32（5）：

384-386.

[9] 周丽华，徐武华. Tau蛋白靶向的阿尔茨海默病免疫

治疗研究现状[J]. 中国神经精神疾病杂志，2017，43

（2）：126-128.

[10] CARRANO A，HOOZEMANS J J，VAN DER VIES

S M，et al. Neuroinflammation and blood-brain

barrier changes in capillary amyloid angiopathy[J].

Neurodegener Dis，2012，10（1-4）：329-331.

[11] SENQILLO J D，WINKLER E A，WALKER C T，

et al. Deficiency in mural vascular cells coincides

with blood-brain barrier disruption in Alzheimer’s

disease[J]. Brain Pathol，2013，23（3）：303-310.

[12] ALAFUZOFF I，ADOLFSSON R，ADOLFSSON R，

et al. Blood-brain barrier in Alzheimer dementia and

in non-demented elderly. An immunocytochemical

study[J]. Acta Neuropathol，1987，73（2）：160-166.

[13] TOMIMOTO H，AKIGUCHI I，SUENAGA T，et

al. Alterations of the blood-brain barrier and glial

cells in white-matter lesions in cerebrovascular and

Alzheimer’s disease patients[J]. Stroke，1996，27

（11）：2069-2074.

[14] SkILLBäCK T，DELSING L，SYNNERGREN J，et

al. CSF/serum albumin ratio in dementias：a crosssectional

study on 1861 patients[J/OL]. Neurobiol

Aging，2017，59：1-9. https：//doi.org/10.1016/

j.neurobiolaging.2017.06.028.

[15] 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.

[16] VAN ASSEMA D M，LUBBERINK M，BAUER M，

et al. Blood-brain barrier P-glycoprotein function

in Alzheimer’s disease[J]. Brain，2012，135（Pt 1）：

181-189.

[17] 徐武华，常铉. 联合预防阿尔茨海默病与缺血性卒中

的构想[J]. 医学与哲学，2014，35（7）：76-77.

[18] SWEENEY MD，SAGARE AP，ZLOKOVIC BV.

Blood-brain barrier breakdown in Alzheimer disease

and other neurodegenerative disorder[J]. Nat Rev

Neurol，2018，14（3）：133-150.

[19] BRUCKMANN S，BRENN A，GRUBE M，et

al. Lack of P-glycoprotein Results in Impairment

of Removal of Beta--Amyloid and Increased

Intraparenchymal Cerebral Amyloid Angiopathy

after Active Immunization in a Transgenic Mouse

Model of Alzheimer’s Disease[J]. Curr Alzheimer

Res，2017，14（6）：656-667.

[20] LIU M，JEVTIC S，MARKHAM-COULTES K，et

al. Investigating the efficacy of a combination Aβ-

targeted treatment in a mouse model of Alzheimer’s

disease[J/OL]. Brain Research，2018，1678：138-145.

https：//doi.org/10.1016/j.brainres.2017.10.015.

[21] RICCIARELLI R，FEDELE E. The amyloid

Cascade Hypothesis in Alzheimer’s disease：It’s

Time to change Our Mind[J]. Curr Neuropharmacol，

2017，15（6）：926-935.

[22] STORCK S E，MEISTER S，NAHRATH J，et al.

Endothelial LRP1 transports amyloid-β（1-42）across

the blood-brain barrier[J]. J Clin Invest，2016，126

（1）：123-136.

[23] SHIBATA M，YAMADA S，KUMAR S R，et al.

Clearance of Alzheimer’s amyloid-ss（1-40）peptide

from brain by LDL receptor-related protein-1 at the

blood-brain barrier[J]. J Clin Invest，2000，106（12）：

1489-1499.

[24] LAM F C，LIU R，LU P，et al. Beta-Amyloid efflux

mediated by p-glycoprotein[J]. J Neurochem，2001，

76（4）：1121-1128.

[25] CARRANO A，SNKHCHYAN H，KOOIJ G，et al.

ATP-binding cassette transporters P-glycoprotein

and breast cancer related protein are reduced in

capillary cerebral amyloid angiopathy[J]. Neurobiol

Aging，2014，35（3）：565-575.

[26] JEYNES B，PROVIAS J. Evidence for altered

LRP/RAGE expression in alzheimer lesion

pathogenesis[J]. Curr Alzheimer Res，2008，5（5）：

432-437.

[27] DEANE R，SINGH I，SAGARE A P，et al. A

Multimodal RAGE-specific inhibitor reduces

amyloid β-mediated brain disorder in a mouse model

of Alzheimer disease[J]. J Clin Invest，2012，122（4）：

1377-1392.

[28] PETRUSHINA I，GHOCHIKYAN A，

MKRTICHYAN M，et al. Mannan-Abeta28

conjugate prevents Abeta-plaque deposition，

but increases microhemorrhages in the brains

of vaccinated Tg2576（APPsw）mice[J/OL]. J

Neuroinflammation，2008，5：42. https：//doi.

org/10.1186/1742-2094-5-42.

[29] BIEN-LY N，BOSWELL C A，JEET S，et al. Lack

of widespread BBB Disruption in Alzheimer’s

Disease Models：Focus on Therapeutic Antibodies[J].

Neuron，2015，88（2）：289-297.