Tao, Rui

Amyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science techniques were used to evaluate PET images, transforming Aβ imaging into topographical pixel arrays for 3D reconstruction. Canal-like networks in the brain, skull, and neck were discovered to be part of the non-CNS fluid (NCF) compartment, which quarantines Aβ. In CU/Aβ- subjects, Aβ is transported to peripheral lymphatics. In AD/Aβ+ subjects, Aβ becomes congested in the NCF, diffusing into CNS interstitial fluid, leading to progression and neurodegeneration.

Unintentional weight loss in older adults often precedes Alzheimer’s disease (AD). Positron emission tomography (PET) scan reveals that AD patients exhibit reduced uptake of fluorodeoxyglucose into brain cells, defined as ‘hypometabolism’. However, cellular mechanisms underlying weight loss and hypometabolism have not received much attention. The primary goal of the study was to test the hypothesis that cells become starved in confrontation with amyloid beta proteins (Aβ), which are increasingly aggregated in the AD brain. Cellular ATP is known as a biomarker indicating for cell starvation. We found that Aβ caused a dose-dependent reduction in ATP of astrocytes. This effect was similar to those of cells being deprived from nutrients (i.e., glucose, pyruvate and glutamine). Together, the data of the present study support the hypothesis that cell starvation is likely associated with weight loss and hypometabolism in AD patients.

The present study aimed at quantifying the topographic distribution of spectral power as measured with electroencephalogram (EEG) in patients with opioid use disorder (OUD) across five broad band frequencies (δ, θ, α, β, and γ). Through comparative groups of healthy controls, patients with methamphetamine use disorder, and patients with alcohol use disorder, it was determined that OUD EEG spectral power was globally increased in the δ frequency, and more region-specific in others (frontal lobes in θ and β frequencies). α frequency was reduced in occipital lobes in OUD. The observed changes are discussed in terms of the microcircuit-level changes in the cortex. Based on these findings, EEG may prove to be a valuable tool for diagnostic and prognostic evaluation of OUD.

This study aimed to identify changes in the expression of serotonin (5-hydroxytryptamine; 5-HT) receptor 5-HT2a mRNA in paraformaldehyde prefixed rat brain tissue after exposure to 3, 4 methylenedioxymethamphetamine (MDMA). Rather than use traditional, time-consuming methods that were highly prone to error, such as the use of radioactive riboprobes, we used recent advancements in the development of rapid in-situ hybridization to our advantage. The use of rapid in-situ hybridization (such as the RNAscope assay) has allowed us to use paraformaldehyde prefixed brain tissue sections, which are more widely available and easier to use, instead of fresh frozen tissue. Here we describe the results from the use of the RNAscope assay to measure the amount of dapB (a bacterial gene), ppiB (a eukaryotic housekeeping gene), and htr2a (a eukaryotic gene coding for 5-HT2A receptors) mRNA.