Is P-glycoprotein Involved in Amyloid-β Elimination Across the Blood–Brain Barrier in Alzheimer’s Disease?

2010 ◽  
Vol 88 (4) ◽  
pp. 443-445 ◽  
Author(s):  
S Ohtsuki ◽  
S Ito ◽  
T Terasaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

scholarly journals Relationship Between Amyloid-β Deposition and Blood–Brain Barrier Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Dong Wang ◽  
Fanglian Chen ◽  
Zhaoli Han ◽  
Zhenyu Yin ◽  
Xintong Ge ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Factors Affecting ◽  
Blood Brain ◽  
Normal Metabolism

Amyloid-β (Aβ) is the predominant pathologic protein in Alzheimer’s disease (AD). The production and deposition of Aβ are important factors affecting AD progression and prognosis. The deposition of neurotoxic Aβ contributes to damage of the blood–brain barrier. However, the BBB is also crucial in maintaining the normal metabolism of Aβ, and dysfunction of the BBB aggravates Aβ deposition. This review characterizes Aβ deposition and BBB damage in AD, summarizes their interactions, and details their respective mechanisms.

scholarly journals No Evidence for Additional Blood–Brain Barrier P-Glycoprotein Dysfunction in Alzheimer's Disease Patients with Microbleeds

2012 ◽  
Vol 32 (8) ◽  
pp. 1468-1471 ◽  
Author(s):  
Daniëlle ME van Assema ◽  
Jeroen DC Goos ◽  
Wiesje M van der Flier ◽  
Mark Lubberink ◽  
Ronald Boellaard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Volume Of Distribution ◽  
Brain Barrier ◽  
Binding Potential ◽  
Amyloid Angiopathy ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission

Decreased blood–brain barrier P-glycoprotein (Pgp) function has been shown in Alzheimer's disease (AD) patients using positron emission tomography (PET) with the radiotracer ( R)-[11C]verapamil. Decreased Pgp function has also been hypothesized to promote cerebral amyloid angiopathy (CAA) development. Here, we used PET and ( R)-[11C]verapamil to assess Pgp function in eighteen AD patients, of which six had microbleeds (MBs), presumably reflecting underlying CAA. No differences were found in binding potential and nonspecific volume of distribution of ( R)-[11C]verapamil between patient groups. These results provide no evidence for additional Pgp dysfunction in AD patients with MBs.

scholarly journals Blood–brain barrier P-glycoprotein function in Alzheimer's disease

Brain ◽  
2011 ◽  
Vol 135 (1) ◽  
pp. 181-189 ◽  
Author(s):  
Daniëlle M. E. van Assema ◽  
Mark Lubberink ◽  
Martin Bauer ◽  
Wiesje M. van der Flier ◽  
Robert C. Schuit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

scholarly journals Alzheimer’s disease: A matter of blood–brain barrier dysfunction?

2017 ◽  
Vol 214 (11) ◽  
pp. 3151-3169 ◽  
Author(s):  
Axel Montagne ◽  
Zhen Zhao ◽  
Berislav V. Zlokovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Neurodegenerative Process ◽  
Blood Brain ◽  
Underlying Mechanisms

The blood–brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer’s disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.

scholarly journals Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

2020 ◽  
Vol 6 (41) ◽  
pp. eabc7031 ◽  
Author(s):  
Yutong Zhou ◽  
Feiyan Zhu ◽  
Yang Liu ◽  
Meng Zheng ◽  
Yibin Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Amyloid Β ◽  
Cognitive Capacity ◽  
Brain Barrier ◽  
Great Promise ◽  
Glucose Transporter 1 ◽  
Blood Brain

Toxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer’s disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated “triple-interaction” stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)–mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This “Trojan horse” strategy supports the utility of RNA interference therapy in neurodegenerative diseases.

Circulating amyloid-β peptide crosses the blood–brain barrier in aged monkeys and contributes to Alzheimer's disease lesions

2002 ◽  
Vol 38 (6) ◽  
pp. 303-313 ◽  
Author(s):  
Jasmina B Mackic ◽  
James Bading ◽  
Jorge Ghiso ◽  
Larry Walker ◽  
Thomas Wisniewski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Amyloid Β Peptide ◽  
Blood Brain

scholarly journals Modulation of amyloid-β aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound

2021 ◽  
Author(s):  
Ramon Vilar ◽  
Tiffany G Chan ◽  
Carmen Ruehl ◽  
Sophie Morse ◽  
Michelle Simon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Complexes ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Amyloid Β ◽  
Binding Mode ◽  
Brain Barrier ◽  
Amyloid Β Peptide ◽  
Blood Brain

One of the key hallmarks of Alzheimer’s disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt...

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