In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease
In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease
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DOI：
10.1007/s00259-010-1612-0
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发表时间：
2011-02-01
影响因子：
9.1
通讯作者：
Ouchi, Yasuomi
中科院分区：
文献类型：
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作者：
Yokokura, Masamichi;Mori, Norio;Ouchi, Yasuomi
淀粉样β蛋白(Aβ)是阿尔茨海默病(AD)的一种病理物质，被认为与一定程度的脑内激活的小胶质细胞共存。然而，目前尚不清楚这两个事件是否与AD体内特有的低代谢同步发生。本研究旨在阐明AD早期特定脑区Aβ蓄积与神经炎症之间的体内关系。11例AD患者在同一天内接受了一系列正电子发射断层扫描(PET)和一系列认知测试。在糖代谢降低的脑区，[C-11](R)PK11195和[C-11]PIB的结合电位(BP)被直接比较。AD患者顶颞区的[C-11](R)PK11195和[C-11]PIB的结合电位显著高于10名健康对照组。在AD患者中，痴呆评分与[C-11](R)PK11195bps呈负相关，而与[C-11]PIB无相关性。直接比较显示[C-11](R)PK11195和[C-11]PIB BP在后扣带回皮质(PCC)呈显著负相关(p<；0.05，校正)，表现出最严重的[F-18]FDG摄取减少。小胶质细胞激活和淀粉样蛋白沉积之间缺乏偶联可能表明，[C-11]PIB显示的Aβ积聚并不总是小胶质细胞激活的主要原因，但PCC中存在的负相关表明，在AD早期，小胶质细胞在产生Aβ时可以表现出更高的激活。
Amyloid beta protein (A beta) is known as a pathological substance in Alzheimer's disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between A beta accumulation and neuroinflammation in those specific brain regions in early AD.Eleven nootropic drug-na < ve AD patients underwent a series of positron emission tomography (PET) measurements with [C-11](R)PK11195, [C-11]PIB and [F-18]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [C-11](R)PK11195 were directly compared with those of [C-11]PIB in the brain regions with reduced glucose metabolism.BPs of [C-11](R)PK11195 and [C-11]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [C-11](R)PK11195 BPs, but not [C-11]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [C-11](R)PK11195 and [C-11]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [F-18]FDG uptake.A lack of coupling between microglial activation and amyloid deposits may indicate that A beta accumulation shown by [C-11]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of A beta in early AD.