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

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. Conclusion: Brain functional connectivity abnormality is correlated with tau pathology in AD and MCI.

Uncovering distinct progression patterns of tau deposition in progressive supranuclear palsy using [18F]Florzolotau PET imaging and subtype/stage inference algorithm

“…The aim was to confirm that all potential participants were devoid of any indicators of intracranial hemosiderin/ferritin, brain tumors, cerebrovascular lesions, or calcification. rs-fMRI images were preprocessed in accordance with the previously reported steps 27 (Data Processing Assistant for Resting-State fMRI ( http://www.rfmri.org/DPARSF )), spatially normalized, and smoothed. 12 , 15 …”

Challenges and Perspectives of Neurological Disorders

“…In the research performed by Ju et al, the authors found that PLFCS and functional connection strength (FCs) were higher in the AD and MCI groups when compared to the normal control group. The study concludes that brain FC abnormality is correlated with tau pathology in AD and MCI [ 10 ].…”