A Robust and Scalable High-Throughput Compatible Assay for Screening Amyloid-β-Binding Compounds.

A robust fluorescent readout assay using topologically-sensitive dyes improves the screening of novel amyloid-binding molecules. One of the key components that make this assay more realistic is the use of endogenous amyloid obtained from 5XFAD mouse brains. The assay conditions were optimized for high throughput screening operation with Z-prime values >0.

Lipopolysaccharide Induced Opening of the Blood Brain Barrier on Aging 5XFAD Mouse Model.

The development of neurotherapeutics for many neurodegenerative diseases has largely been hindered by limited pharmacologic penetration across the blood-brain barrier (BBB). Previous attempts to target and clear amyloid-β (Aβ) plaques, a key mediator of neurodegenerative changes in Alzheimer's disease (AD), have had limited clinical success due to low bioavailability in the brain because of the BBB. Here we test the effects of inducing an inflammatory response to disrupt the BBB in the 5XFAD transgenic mouse model of AD.

In vivo evaluation of IGF1R/IR PET ligand [F]BMS-754807 in rodents.

In vivo evaluation of [F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species.

Aerosol Delivery of Curcumin Reduced Amyloid-β Deposition and Improved Cognitive Performance in a Transgenic Model of Alzheimer's Disease.

We report a novel approach for the delivery of curcumin to the brain via inhalation of the aerosol for the potential treatment of Alzheimer's disease. The percentage of plaque fraction in the subiculum and hippocampus reduced significantly when young 5XFAD mice were treated with inhalable curcumin over an extended period of time compared to age-matched nontreated counterparts. Further, treated animals demonstrated remarkably improved overall cognitive function, no registered systemic or pulmonary toxicity associated with inhalable curcumin observed during the course of this work.

Toxicity studies of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide) as a colonoscopic imaging agent in rats.

Unlabelled: We are investigating an imaging agent that detects early-stage primary colorectal cancer on the mucosal surface in real time under colonoscopic observation. The imaging agent, which is named the nanobeacon, is fluorescent nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide). Its potential use as an imaging tool for colorectal cancer has been thoroughly validated in numerous studies.

Inhalable curcumin: offering the potential for translation to imaging and treatment of Alzheimer's disease.

Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer's disease. Beyond its ability to bind to amyloid plaques, the compound can also cross the blood-brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use.

Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.

Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis.

Identification of promethazine as an amyloid-binding molecule using a fluorescence high-throughput assay and MALDI imaging mass spectrometry.

The identification of amyloid-binding compounds is a crucial step in the development of imaging probes and therapeutics for the detection and cure of Alzheimer's disease. Unfortunately, the process typically lags during the translation from in vitro to in vivo studies due to the impenetrable nature of the blood brain barrier (BBB). Here, we integrate fluorescence assay with MALDI imaging mass spectrometry to screen known compounds and repurpose their properties to enable the second function of binding to amyloid plaques.

Randomized controlled trial of the Breast Cancer Recovery Program for women with breast cancer-related lymphedema.

Evidence-based exercise and relaxation recommendations for people with breast cancer-related lymphedema (BCRL) are needed. We report a randomized controlled study of one program, designed to achieve synergistic improvements in physical and emotional BCRL symptoms. People in the treatment group received an exercise and relaxation program, The Breast Cancer Recovery Program (N=16).

Molecular neurodevelopment: an in vivo 31P-1H MRSI study.

Synaptic development and elimination are normal neurodevelopmental processes, which if altered could contribute to various neuropsychiatric disorders. 31P-1H magnetic resonance spectroscopic imaging (MRSI) and structural magnetic resonance imaging (MRI) exams were conducted on 105 healthy children ages 6-18 years old to identify neuromolecular indices of synaptic development and elimination. Over the age range studied, age-related changes in high-energy phosphate (phosphocreatine), membrane phospholipid metabolism (precursors and breakdown products), and percent gray matter volume were found.

Interactions of Abeta(1-40) with glycerophosphocholine and intact erythrocyte membranes: fluorescence and circular dichroism studies.

Deposition of amyloid beta peptide in human brain in the form of senile plaques is a neuropathological hallmark of Alzheimer's disease (AD). Levels of a phospholipid breakdown product, glycerophosphocholine (GPC), also increase in AD brain. The effect of GPC on amyloid beta(1-40) peptide (Abeta) aggregation in PBS buffer was investigated by circular dichroism and fluoresence spectroscopy; interactions of Abeta and GPC with the intact erythrocyte membrane was examined by fluoresence spectroscopy.

Effect of intraperitoneal acetyl-L-carnitine (ALCAR) on anxiety-like behaviours in rats.

Acetyl-L-carnitine (ALCAR) is an acetyl derivative of carnitine, an endogenous molecule synthesized in vivo and supplemented by diet (mainly via meat and dairy products). Several parallel, double-blind, placebo-controlled studies have demonstrated that ALCAR treatment produces beneficial effects in geriatric depression. Since most antidepressants also have anti-anxiety effects we examined whether ALCAR shows anti-anxiety effects in a rat model of anxiety.

Acetyl-l-carnitine as a possible therapy for Alzheimer's disease.

Alterations have been demonstrated in membrane phospholipid metabolism in Alzheimer's disease. Alterations in membrane phospholipid metabolite levels have been observed by 31P magnetic resonance spectroscopy 4 years before onset of cognitive changes. Implications of phospholipid membrane changes in Alzheimer's disease are presented.

31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results.

Objective: This 12-week study of two elderly, depressed subjects investigated the effect of acetyl-L-carnitine (ALCAR) treatment on the Hamilton Depression Rating Scale (HDRS) and on measures of high-energy phosphate and membrane phospholipid metabolism.

Methods: Two mildly depressed (HDRS 15-20), non-demented male subjects 70 and 80 years old were compared with six non-demented controls (all males, mean age of 73.6 +/- 3.

Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology.

Background: The presence of psychotic symptoms in Alzheimer Disease subjects (AD+psychosis, AD+P) is a marker for a phenotype characterized by more severe cognitive impairment and a more rapidly deteriorating course. Although AD+P has been inconsistently associated with more severe neuropathology, no prior studies have examined measures of neuronal and synaptic integrity.

Objective: To determine whether AD+P is associated with evidence of disrupted neuronal and synaptic integrity, as indicated by magnetic resonance spectroscopy (MRS) measurement of N-acetyl-L-aspartate and the membrane breakdown products, glycerophosphocholine and glycerophosphoethanolamine.