体内tau蛋白负荷与阿尔茨海默病中异常脑功能连接的相关性：一项F-Florzolotau研究
In Vivo Tau Burden Is Associated with Abnormal Brain Functional Connectivity in Alzheimer's Disease: A F-Florzolotau Study.
作者信息
Ju Zizhao, Li Zhuoyuan, Lu Jiaying, Jiao Fangyang, Lin Huamei, Bao Weiqi, Li Ming, Wu Ping, Guan Yihui, Zhao Qianhua, Zhang Huiwei, Jiang Jiehui, Zuo Chuantao
机构信息
PET Center and National Research Center for Aging and Medicine & National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200035, China.
School of Communication and Information Engineering, Shanghai University, Shanghai 200444, China.
出版信息
Brain Sci. 2022 Oct 6;12(10):1355. doi: 10.3390/brainsci12101355.
PURPOSE
F-Florzolotau is a novel second-generation tau radiotracer that shows higher binding affinity and selectivity and no off-target binding. The proportion loss of functional connectivity strength (PLFCS) is a new indicator for representing brain functional connectivity (FC) alteration. This study aims to estimate the relationship between the regional tau accumulation and brain FC abnormality in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients based on Florzolotau PET and fMRI.
METHODS
22 NC (normal control), 31 MCI and 42 AD patients who have already been scanned with F-Florzolotau PET were recruited in this study. (We calculated the PLFCS and standardized uptake value ratio (SUVR) of each node based on the Brainnetome atlas (BNA) template. The SUVR of 246 brain regions was calculated with the cerebellum as the reference region. Further functional connection strength (FCs), PLFCS and SUVR of each brain region were obtained in three groups for comparison.) For each patient, PLFCS and standardized uptake value ratio (SUVR) were calculated based on the Brainnetome atlas (BNA) template. These results, as well as functional connection strength (FCs), were then compared between different groups. Multiple permutation tests were used to determine the target nodes between NC and cognitive impairment (CI) groups (MCI and AD). The relationship between PLFCS and neuropsychological scores or cortical tau deposit was investigated via Pearson correlation analysis.
RESULTS
Higher PLFCS and FCs in AD and MCI groups were found compared to the NC group. The PLFCS of 129 brain regions were found to be different between NC and CI groups, and 8 of them were correlated with tau SUVR, including superior parietal lobule (MCI: = 0.4360, = 0.0260, AD: = -0.3663, = 0.0280), middle frontal gyrus (AD: MFG_R_7_2: = 0.4106, = 0.0129; MFG_R_7_5: = 0.4239, = 0.0100), inferior frontal gyrus (AD: IFG_R_6_2: = 0.3589, = 0.0316), precentral gyrus (AD: PrG_R_6_6: = 0.3493, = 0.0368), insular gyrus (AD: INS_R_6_3: = 0.3496, = 0.0366) and lateral occipital cortex (AD: LOcC _L_4_3: = -0.3433, = 0.0404). Noteworthily, the opposing relationship was found in the superior parietal lobule in the MCI and AD groups.
CONCLUSIONS
Brain functional connectivity abnormality is correlated with tau pathology in AD and MCI.
目的
F-Florzolotau是一种新型的第二代tau放射性示踪剂，具有更高的结合亲和力和选择性，且无脱靶结合。功能连接强度比例损失（PLFCS）是一种用于表示脑功能连接（FC）改变的新指标。本研究旨在基于Florzolotau正电子发射断层扫描（PET）和功能磁共振成像（fMRI）评估阿尔茨海默病（AD）和轻度认知障碍（MCI）患者区域tau蛋白积聚与脑FC异常之间的关系。
方法
本研究招募了22名正常对照（NC）、31名MCI患者和42名已接受F-Florzolotau PET扫描的AD患者。（我们基于脑网络组图谱（BNA）模板计算每个节点的PLFCS和标准化摄取值比率（SUVR）。以小脑为参考区域计算246个脑区的SUVR。进而在三组中获取每个脑区的功能连接强度（FCs）、PLFCS和SUVR进行比较。）对于每位患者，基于BNA模板计算PLFCS和标准化摄取值比率（SUVR）。然后在不同组之间比较这些结果以及功能连接强度（FCs）。采用多次置换检验确定NC组与认知障碍（CI）组（MCI和AD）之间的目标节点。通过Pearson相关分析研究PLFCS与神经心理学评分或皮质tau蛋白沉积之间的关系。
结果
与NC组相比，AD组和MCI组的PLFCS和FCs更高。发现NC组与CI组之间129个脑区的PLFCS存在差异，其中8个与tau SUVR相关，包括顶上小叶（MCI： = 0.4360， = 0.0260，AD： = -0.3663， = 0.0280）、额中回（AD：MFG_R_7_2： = 0.4106， = 0.0129；MFG_R_7_5： = 0.4239， = 0.0100）、额下回（AD：IFG_R_6_2： = 0.3589， = 0.0316）、中央前回（AD：PrG_R_6_6： = 0.3493， = 0.0368）、脑岛（AD：INS_R_6_3： = 0.3496， = 0.0366）和枕外侧皮质（AD：LOcC _L_4_3： = -0.3433， = 0.0404）。值得注意的是，在MCI组和AD组的顶上小叶中发现了相反的关系。
结论
AD和MCI中的脑功能连接异常与tau病理相关。
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