کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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329446 | 1433628 | 2009 | 7 صفحه PDF | دانلود رایگان |

Cerebrovascular P-glycoprotein (P-gp) acts at the blood–brain barrier (BBB) as an active cell membrane efflux pump for several endogenous and exogenous compounds. Age-associated decline in P-gp function could facilitate the accumulation of toxic substances in the brain, thus increasing the risk of neurodegenerative pathology with aging. We hypothesised a regionally reduced BBB P-gp function in older healthy subjects.We studied cerebrovascular P-gp function using [11C]-verapamil positron emission tomography (PET) in seventeen healthy volunteers with age 18–86. Logan analysis was used to calculate the distribution volume (DV) of [11C]-verapamil in the brain. Statistical Parametric Mapping was used to study specific regional differences between the older compared with the younger adults.Older subjects showed significantly decreased P-gp function in internal capsule and corona radiata white matter and in orbitofrontal regions.Decreased BBB P-gp function in those regions could thus explain part of the vulnerability of the aging brain to white matter degeneration. Moreover, decreased BBB P-gp function with aging could be a mechanism by which age acts as the main risk factor for the development of neurodegenerative disease.
Journal: Neurobiology of Aging - Volume 30, Issue 11, November 2009, Pages 1818–1824