Esposito Giuseppe, Giovacchini Giampiero, Liow Jeih-San, Bhattacharjee Abesh K, Greenstein Dede, Schapiro Mark, Hallett Mark, Herscovitch Peter, Eckelman William C, Carson Richard E, Rapoport Stanley I
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Nucl Med. 2008 Sep;49(9):1414-21. doi: 10.2967/jnumed.107.049619. Epub 2008 Aug 14.
Incorporation coefficients (K*) of arachidonic acid (AA) in the brain are increased in a rat model of neuroinflammation, as are other markers of AA metabolism. Data also indicate that neuroinflammation contributes to Alzheimer's disease (AD). On the basis of these observations, K* for AA was hypothesized to be elevated in patients with AD.
A total of 8 patients with AD with an average (+/-SD) Mini-Mental State Examination score of 14.7+/-8.4 (mean age, 71.7+/-11.2 y) and 9 controls with a normal Mini-Mental State Examination score (mean age, 68.7+/-5.6 y) were studied. Each subject received a (15)O-water PET scan of regional cerebral blood flow, followed after 15 min by a 1-(11)C-AA scan of regional K* for AA.
In the patients with AD, compared with control subjects, global gray matter K* for AA (corrected or uncorrected for the partial-volume error [PVE]) was significantly elevated, whereas only PVE-uncorrected global cerebral blood flow was reduced significantly (P<0.05). A false-discovery-rate procedure indicated that PVE-corrected K* for AA was increased in 78 of 90 identified hemispheric gray matter regions. PVE-corrected regional cerebral blood flow, although decreased in 12 regions at P<0.01 by an unpaired t test, did not survive the false-discovery-rate procedure. The surviving K* increments were widespread in the neocortex but were absent in caudate, pallidum, and thalamic regions.
These preliminary results show that K* for AA is widely elevated in the AD brain, particularly in regions reported to have high densities of senile (neuritic) plaques with activated microglia. To the extent that the elevations represent upregulated AA metabolism associated with neuroinflammation, PET with 1-(11)C-AA could be used to examine neuroinflammation in patients with AD and other brain diseases.
在神经炎症大鼠模型中，大脑中花生四烯酸（AA）的掺入系数（K*）升高，AA代谢的其他标志物也是如此。数据还表明神经炎症与阿尔茨海默病（AD）有关。基于这些观察结果，推测AD患者的AA的K*升高。
研究了8例AD患者，其简易精神状态检查表平均（±标准差）得分为14.7±8.4（平均年龄，71.7±11.2岁），以及9例简易精神状态检查表得分正常的对照者（平均年龄，68.7±5.6岁）。每位受试者接受一次用（15）O-水进行的局部脑血流PET扫描，15分钟后再接受一次用1-（11）C-AA进行的AA局部K*扫描。
与对照者相比，AD患者中，AA的全脑灰质K*（针对部分容积误差[PVE]进行校正或未校正）显著升高，而仅未校正PVE的全脑血流显著降低（P<0.05）。错误发现率程序表明，在90个已识别的半球灰质区域中的78个区域，校正PVE后的AA的K升高。校正PVE后的局部脑血流，虽然通过不成对t检验在12个区域中P<0.01时降低，但未通过错误发现率程序检验。存活下来的K升高在新皮质中广泛存在，但在尾状核、苍白球和丘脑区域不存在。
这些初步结果表明，AD大脑中AA的K*广泛升高，特别是在据报道有高密度伴有活化小胶质细胞的老年（神经炎性）斑块的区域。就这些升高代表与神经炎症相关的上调的AA代谢而言，用1-（11）C-AA进行PET可用于检查AD患者和其他脑部疾病患者的神经炎症。
