In Vivo Tau Burden Is Associated with Abnormal Brain Functional Connectivity in Alzheimer's Disease: A 18F-Florzolotau Study

Zizhao Ju; Zhuoyuan Li; Jiaying Lu; Fangyang Jiao; Huamei Lin; Weiqi Bao; Ming Li; Ping Wu; Yihui Guan; Qianhua Zhao; Huiwei Zhang; Jiehui Jiang; Chuantao Zuo

doi:10.3390/brainsci12101355

In Vivo Tau Burden Is Associated with Abnormal Brain Functional Connectivity in Alzheimer's Disease: A ¹⁸F-Florzolotau Study

Brain Sci. 2022 Oct 6;12(10):1355. doi: 10.3390/brainsci12101355.

Authors

Zizhao Ju¹, Zhuoyuan Li², Jiaying Lu¹, Fangyang Jiao¹, Huamei Lin¹, Weiqi Bao¹, Ming Li¹, Ping Wu¹, Yihui Guan¹, Qianhua Zhao³, Huiwei Zhang¹, Jiehui Jiang⁴, Chuantao Zuo¹

Affiliations

¹ PET Center and National Research Center for Aging and Medicine & National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200035, China.
² School of Communication and Information Engineering, Shanghai University, Shanghai 200444, China.
³ Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
⁴ Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai 200444, China.

Abstract

Purpose: ¹⁸F-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 ¹⁸F-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: r = 0.4360, p = 0.0260, AD: r = -0.3663, p = 0.0280), middle frontal gyrus (AD: MFG_R_7_2: r = 0.4106, p = 0.0129; MFG_R_7_5: r = 0.4239, p = 0.0100), inferior frontal gyrus (AD: IFG_R_6_2: r = 0.3589, p = 0.0316), precentral gyrus (AD: PrG_R_6_6: r = 0.3493, p = 0.0368), insular gyrus (AD: INS_R_6_3: r = 0.3496, p = 0.0366) and lateral occipital cortex (AD: LOcC _L_4_3: r = -0.3433, p = 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.

Keywords: Alzheimer’s disease; Florzolotau PET; functional connectivity; mild cognitive impairment.

Abstract

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