Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer’s Disease: A PET (THK5351, PiB) and Resting fMRI Study

Abstract

Background: Imaging studies in Alzheimer’s disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls.Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls.Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC.Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

Graph theory analysis of resting‐state functional magnetic resonance imaging in essential tremor

“…Specifically, ET patients are characterized by lower small-worldness values of the network-less clustered functionality of the brain-together with altered connectivity patterns in specific systems. False discovery rate correction for multiple comparisons was applied to the significance level for the correlation contrasts between the significant ROIs T A B L E 4 Regional graph topological differences and its relationship with the pathogenesis of ET (Yokoi et al, 2018) Older-onset ET is associated not only with higher odds of prevalent Alzheimer's disease (Benito-León et al, 2006a), but also with an increased risk of Alzheimer's disease Frontal operculum This is a key node in a network for exerting control over cognitive processes (Higo, Mars, Boorman, Buch, & Rushworth, 2011) Cognitive deficits have been described in ET (Benito-León et al, 2006b). At the regional level, we found the existence of multiple connectivity differences between ET patients and healthy controls in motor and extramotor related areas.…”

Quantitation of in vivo brain glutathione conformers in cingulate cortex among age‐matched control, MCI, and AD patients using MEGA‐PRESS

“…The cingulate area, especially PCC, is one of the earliest regions to exhibit hypometabolism (Mosconi, 2005). Studies on differential susceptibility using PET reported hypometabolism in PCC, but not in the ACC region of early AD (Minoshima et al, 1997;Yokoi et al, 2018) and also in MCI patients (Tomadesso et al, 2015). However, few studies have reported a significant hypometabolism in both the ACC and PCC regions in AD (Bailly et al, 2015;Chetelat et al, 2008;Hauser et al, 2013) as well as in apolipoprotein E (APOE) carriers, when compared to noncarriers (Langbaum et al, 2010).…”

Hypoperfusion in the posterior cingulate cortex is associated with lower bone mass density in elderly women with osteopenia and Alzheimer’s disease

“…Studies have shown that these same parietal and limbic areas—which are associated with the executive attention and multi‐tasking networks—are selectively affected in mild AD and overlap with regional patterns of brain atrophy, glucose hypometabolism, and hypoperfusion . Furthermore, brain regions showing early amyloid and tau protein deposits overlap with posterior parts of the cognitive control and default mode networks . We interpret these findings as suggesting at least in part, a common pathological mechanism in AD that contributes to both bone loss and decreased functional connectivity in the left PCC.…”