Blood-Brain Barrier ABC-transporter P-glycoprotein in Alzheimer's Disease: Still a Suspect?

2016 ◽  
Vol 22 (38) ◽  
pp. 5808-5816 ◽  
Author(s):  
Danielle Assema ◽  
Bart Berckel
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 ◽  
...  

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.


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 ◽  
...  

2012 ◽  
Vol 8 (4S_Part_19) ◽  
pp. P698-P698
Author(s):  
Anand Deo ◽  
Soo Borson ◽  
Jeanne Link ◽  
Janet Eary ◽  
Todd Richards ◽  
...  

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 ◽  
...  

NeuroImage ◽  
2010 ◽  
Vol 52 ◽  
pp. S53 ◽  
Author(s):  
Danielle M.E. van Assema ◽  
Mark Lubberink ◽  
Nikie J. Hoetjes ◽  
Harry H. Hendrikse ◽  
Robert C. Schuit ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Anja Brenn ◽  
Markus Grube ◽  
Michele Peters ◽  
Andrea Fischer ◽  
Gabriele Jedlitschky ◽  
...  

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.


2012 ◽  
Vol 2 (1) ◽  
pp. 57 ◽  
Author(s):  
Daniëlle ME van Assema ◽  
Mark Lubberink ◽  
Patrizia Rizzu ◽  
John C van Swieten ◽  
Robert C Schuit ◽  
...  

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