War Related Illness and Injury Study Center, VA Palo Alto Health Care System and Department of Psychiatry & Behavioral Sciences, Stanford University, Palo Alto, USA.
J Alzheimers Dis. 2019;68(1):77-83. doi: 10.3233/JAD-181198.
In this issue, an article by Tiepolt et al. shows that PET scanning using [11C]PiB can demonstrate both cerebral blood flow (CBF) changes and amyloid-β (Aβ) deposition in patients with mild cognitive dysfunction or mild dementia of Alzheimer's disease (AD). The CBF changes can be determined because the early scan counts (1-9 minutes) reflect the flow of the radiotracer in the blood passing through the brain, while the Aβ levels are measured by later scan counts (40-70 minutes) after the radiotracer has been cleared from regions to which the radiotracer did not bind. Thus, two different diagnostic measures are obtained with a single injection. Unexpectedly, the mild patients with Aβ positivity had scan data with only a weak relationship to memory, while the relationships to executive function and language function were relatively strong. This divergence of findings from studies of severely impaired patients highlights the importance of determining how AD pathology affects the brain. A possibility suggested in this commentary is that Aβ deposits occur early in AD and specifically in critical areas of the neocortex affected only later by the neurofibrillary pathology indicating a different role of the amyloid-β protein precursor (AβPP) in the development of those neocortical regions, and a separate component of AD pathology may selectively impact functions of these neocortical regions. The effects of adverse AβPP metabolism in the medial temporal and brainstem regions occur later possibly because of different developmental issues, and the later, different pathology is clearly more cognitively and socially devastating.
本期发表了一篇由 Tiepolt 等人撰写的文章，表明使用[11C]PiB 的正电子发射断层扫描（PET）不仅可以显示出轻度认知功能障碍或阿尔茨海默病（AD）轻度痴呆患者的脑血流（CBF）变化，还可以显示出淀粉样蛋白-β（Aβ）沉积。之所以能够确定 CBF 变化，是因为早期扫描计数（1-9 分钟）反映了放射性示踪剂在流经大脑的血液中的流动情况，而 Aβ 水平则通过放射性示踪剂从未结合放射性示踪剂的区域清除后的后期扫描计数（40-70 分钟）来测量。因此，单次注射即可获得两种不同的诊断测量值。出乎意料的是，Aβ 阳性的轻度患者的扫描数据与记忆的相关性较弱，而与执行功能和语言功能的相关性相对较强。与严重受损患者的研究结果的这种差异突出表明，需要确定 AD 病理学如何影响大脑。本文评论中提出的一种可能性是，Aβ 沉积在 AD 中发生较早，并且仅在随后影响神经纤维病理的新皮层关键区域发生，这表明淀粉样蛋白-β 蛋白前体（AβPP）在这些新皮层区域的发展中具有不同的作用，AD 病理学的另一个组成部分可能会选择性地影响这些新皮层区域的功能。内侧颞叶和脑干区域中不利的 AβPP 代谢的影响发生较晚，可能是因为存在不同的发育问题，而较晚发生的不同病理学显然对认知和社交能力具有更大的破坏性。
