Bartels Anna L, Kortekaas Rudie, Bart Joost, Willemsen Antoon T M, de Klerk Onno L, de Vries Jeroen J, van Oostrom Joost C H, Leenders Klaus L
Department of Neurology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Neurobiol Aging. 2009 Nov;30(11):1818-24. doi: 10.1016/j.neurobiolaging.2008.02.002. Epub 2008 Mar 20.
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 [(11)C]-verapamil positron emission tomography (PET) in seventeen healthy volunteers with age 18-86. Logan analysis was used to calculate the distribution volume (DV) of [(11)C]-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.
脑血管P-糖蛋白（P-gp）在血脑屏障（BBB）处作为多种内源性和外源性化合物的活性细胞膜外排泵发挥作用。P-gp功能随年龄增长而下降可能会促进有毒物质在大脑中的积累，从而增加衰老过程中神经退行性病变的风险。我们假设在健康的老年受试者中，血脑屏障P-gp功能存在区域性降低。我们使用[(11)C]-维拉帕米正电子发射断层扫描（PET）对17名年龄在18-86岁的健康志愿者的脑血管P-gp功能进行了研究。采用Logan分析法计算[(11)C]-维拉帕米在大脑中的分布容积（DV）。使用统计参数映射法研究老年受试者与年轻受试者之间的特定区域差异。老年受试者在内囊、放射冠白质和眶额区域的P-gp功能显著降低。这些区域血脑屏障P-gp功能的降低可能解释了衰老大脑对白质变性易感性的部分原因。此外，随着年龄增长血脑屏障P-gp功能降低可能是年龄成为神经退行性疾病发展主要危险因素的一种机制。
