Pharmacodynamic and Toxicity Studies of 6-Isopropyldithio-2'-guanosine Analogs in Acute T-Lymphoblastic Leukemia.

(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010.

Brain health correlates of mobility-related confidence.

Background: Mobility is important for independence in older age. While brain health correlates of objectively measured mobility-related features like gait and balance have been reported, we aimed to test neuroimaging and cognitive correlates of subjective measures of mobility-related confidence.

Methods: We carried out a cross-sectional observational study comprised of N = 29 cognitively unimpaired older adult participants, mean age 75.

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans.

The Alzheimer's Disease Neuroimaging Initiative showed that Japanese had significantly lower brain Aβ burden than Americans among a cognitively normal population. This cross-sectional study aimed to compare vascular disease burden, Aβ burden, and neurodegeneration between cognitively normal elderly Japanese and Americans. Japanese and American participants were matched for age (±4-year-old), sex, and Apolipoprotein E () genotype.

Associations of equol-producing status with white matter lesion and amyloid-β deposition in cognitively normal elderly Japanese.

Introduction: Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti-oxidant and anti-amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aβ) deposition.

Methods: From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using C-Pittsburgh compound-B.

Influence of apolipoprotein-E genotype on brain amyloid load and longitudinal trajectories.

To characterize the influence of apolipoprotein-E (APOE) genotype on cerebral Aβ load and longitudinal Aβ trajectories, [C]Pittsburgh compound-B (PiB) positron emission tomography (PET) imaging was used to assess amyloid load in a clinically heterogeneous cohort of 428 elderly participants with known APOE genotype. Serial [C]PiB data and a repeated measures model were used to model amyloid trajectories in a subset of 235 participants classified on the basis of APOE genotype. We found that APOE-ε4 was associated with increased Aβ burden and an earlier age of onset of Aβ positivity, whereas APOE-ε2 appeared to have modest protective effects against Aβ.

Associations between NIH Toolbox Cognition Battery and brain amyloid and tau pathology in non-demented older adults.

Introduction: The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) was developed to be a common assessment metric across a broad array of research studies. We investigated associations between NIHTB-CB and brain amyloid and tau deposition in cognitively unimpaired older adults.

Methods: One hundred eighteen community-based volunteers completed magnetic resonance imaging (MRI), Pittsburgh compound B (PiB)-PET (positron emission tomography) and AV-1451-PET neuroimaging, a neuropsychological evaluation, NIHTB-CB, and the Clinical Dementia Rating (CDR) scale.

Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population.

The use of Centiloids for applying [C]PiB classification cutoffs across region-of-interest delineation methods.

Introduction: Centiloid standardization was developed to establish a quantitative outcome measure of amyloid burden that could accommodate the integration of different amyloid positron emission tomography radiotracers or different methods of quantifying the same tracer. The goal of this study was to examine the use of Centiloids for establishing amyloid classification cutoffs for differing region-of-interest (ROI) delineation schemes.

Methods: Using ROIs from hand-drawn delineation in native space as the gold standard, we compared standard uptake value ratios obtained from the 6 hand-drawn ROIs that determine amyloid-positivity classification with standard uptake value ratio obtained from 3 different automated techniques (FreeSurfer, Statistical Parametric Mapping, and superimposed hand-drawn ROIs in Pittsburgh Compound B template space).

Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk.

The synergistic effect between β-amyloid(1-42) and α-synuclein on the synapses dysfunction in hippocampal neurons.

Objective: This study was to explore the molecular mechanisms underpinning the synergetic effect between β-amyloid (Aβ) and α-synuclein (α-syn) on synapses dysfunction during the development of neurodegenerative disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Alzheimer disease (AD).

Methods: The primary cultured hippocampal neurons prepared from the fetal tissue of mice were divided into six groups and treated with DMSO, Aβ(42-1), α-syn, Aβ(1-42), α-syn plus Aβ(42-1) and α-syn plus Aβ(1-42), respectively. After incubation for 24 h, the synapsin I content was calculated by immunofluorescence and the synaptic vesicle recycling was monitored by FM1-43 staining.