The Precuneus – A Witness for Excessive Aβ Gathering in Alzheimer’s Disease Pathology

Abstract

Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [¹⁸F]-flor­betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.

An Improved Multi-Task Sparse Canonical Correlation Analysis of Imaging Genetics for Detecting Biomarkers of Alzheimer’s Disease

“…These QTs have been reported in the past. It was confirmed in [22][23][24]. The JSCCA algorithm did not The critical roles of apoptosis and hepatitis B in the process of AD were confirmed in the literature [31][32].…”

Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex

“…Metabolic reduction or hypoperfusion of the PC can be found in the early stages of AD, even before clinical diagnosis of dementia ( Thomas et al, 2019 ). It is possible that hypoperfusion begins largely in PC and spreads to the parietal cortex and cingulate gyrus along with progression of the AD to other cortical areas ( Aghakhanyan et al, 2018 ). The PC is involved in working memory and its deactivation is associated with early MCI assessed by a validated clinical screening instrument for cognitive decline ( Yokosawa et al, 2020 ).…”

“…The PC is involved in working memory and its deactivation is associated with early MCI assessed by a validated clinical screening instrument for cognitive decline ( Yokosawa et al, 2020 ). Moreover, the PC seems to be a region with high vulnerability to β-amyloid (Aβ) deposition, showing major Aβ load in Aβ-PET and in association with cognitive decline in MCI and AD patients compared with healthy controls ( Aghakhanyan et al, 2018 ). White matter microstructure alteration occurs in the early stage of amyloid pathology and the strongest association was found in PC and the corpus callosum ( Collij et al, 2021 ).…”

Telomeric alterations in the default mode network during the progression of Alzheimer’s disease: Selective vulnerability of the precuneus

“…The precuneus (PreC) corresponds to the mesial portion of Brodmann Area (BA) 7 and is a hub of the default mode network (DMN) that also includes frontal (BA10), inferior temporal (BA20) and posterior cingulate (BA23) cortices, which are compromised during the early stages of AD 1‐4 . PreC imaging studies show marked hypometabolism 5‐10 and extensive amyloid ligand binding in both mild cognitive impairment (MCI), a prodromal AD stage and frank AD 1,11,12 . However, this DMN node displays a resilience to synaptic loss, 13 maintenance of neurotrophic proteins 1,3 and limited numbers of neurofibrillary tangles (NFTs) during the onset of AD 3,14 .…”

“…However, this DMN node displays a resilience to synaptic loss, 13 maintenance of neurotrophic proteins 1,3 and limited numbers of neurofibrillary tangles (NFTs) during the onset of AD 3,14 . Despite evidence of early cellular and metabolic dysregulation and resilience to neuropathology, 8,12 very little is known about alterations in cellular chromosomal ribonucleoproteins, telomeres, in prodromal AD. In this regard, mounting evidence suggests that telomeres and telomere maintenance proteins, which modulate neuronal responses to both oxidative stress and DNA damage, 15‐18 are novel therapeutic targets 17,19 and biomarkers for AD 20,21 .…”