Decreased blood–brain barrier expression of P-glycoprotein in Alzheimer’s disease: impact on pathogenesis and brain access of therapeutic agents

2011 ◽  
Vol 2 (7) ◽  
pp. 841-844 ◽  
Author(s):  
Joseph A Nicolazzo ◽  
William A Banks
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Therapeutic Agents ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Disease Impact

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

P4-176: Activity of P-glycoprotein, an ABC efflux transporter at the blood-brain barrier, is compromised in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_19) ◽  
pp. P698-P698
Author(s):  
Anand Deo ◽  
Soo Borson ◽  
Jeanne Link ◽  
Janet Eary ◽  
Todd Richards ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Efflux Transporter ◽  
P Glycoprotein ◽  
Blood Brain

O1-07-04: Blood-brain barrier p-glycoprotein function in Alzheimer's disease

2011 ◽  
Vol 7 ◽  
pp. S110-S110 ◽  
Author(s):  
Danielle M.E. van Assema ◽  
Philip Scheltens ◽  
Bart N.M. van Berckel ◽  
Wiesje M. Flier ◽  
Nelleke Tolboom ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

Decreased P-glycoprotein function at the blood–brain barrier in patients with Alzheimer's disease as shown by (R)-[11C]verapamil and PET

NeuroImage ◽  
2010 ◽  
Vol 52 ◽  
pp. S53 ◽  
Author(s):  
Danielle M.E. van Assema ◽  
Mark Lubberink ◽  
Nikie J. Hoetjes ◽  
Harry H. Hendrikse ◽  
Robert C. Schuit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain

scholarly journals Beta-Amyloid Downregulates MDR1-P-Glycoprotein (Abcb1) Expression at the Blood-Brain Barrier in Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Anja Brenn ◽  
Markus Grube ◽  
Michele Peters ◽  
Andrea Fischer ◽  
Gabriele Jedlitschky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Amyloid Angiopathy ◽  
Amyloid A ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

Neurovascular dysfunction is an important component of Alzheimer's disease, leading to reduced clearance across the blood-brain barrier and accumulation of neurotoxicβ-amyloid (Aβ) peptides in the brain. It has been shown that the ABC transport protein P-glycoprotein (P-gp, ABCB1) is involved in the export of Aβfrom the brain into the blood. To determine whether Aβinfluences the expression of key Aβtransporters, we studied the effects of 1-day subcutaneous Aβ1-40 and Aβ1-42 administration via Alzet mini-osmotic pumps on P-gp, BCRP, LRP1, and RAGE expression in the brain of 90-day-old male FVB mice. Our results demonstrate significantly reduced P-gp, LRP1, and RAGE mRNA expression in mice treated with Aβ1-42 compared to controls, while BCRP expression was not affected. The expression of the four proteins was unchanged in mice treated with Aβ1-40 or reverse-sequence peptides. These findings indicate that, in addition to the age-related decrease of P-gp expression, Aβ1-42 itself downregulates the expression of P-gp and other Aβ-transporters, which could exacerbate the intracerebral accumulation of Aβand thereby accelerate neurodegeneration in Alzheimer's disease and cerebralβ-amyloid angiopathy.

scholarly journals Blood–brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene

2012 ◽  
Vol 2 (1) ◽  
pp. 57 ◽  
Author(s):  
Daniëlle ME van Assema ◽  
Mark Lubberink ◽  
Patrizia Rizzu ◽  
John C van Swieten ◽  
Robert C Schuit ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Healthy Subjects ◽  
Brain Barrier ◽  
Abcb1 Gene ◽  
P Glycoprotein ◽  
Blood Brain
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