Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Tiny worm mimics key genetic risk for Alzheimer’s

Tiny worm mimics key genetic risk for Alzheimer’s

Tiny worm mimics key genetic risk for Alzheimer’s
Student researchers in the Caldwell lab who were co-authors on the latest paper include, from left, Madeline Vaji, Samuel Scopel and Ryan Tuckey. Credit: University of Alabama in Tuscaloosa

Researchers at The University of Alabama have shown a tiny worm can replicate genetic causes of Alzheimer’s disease, expanding the breadth of preclinical models for the disease.

“This is exciting because it validates the idea that we can use this simple system as a way to more rapidly tease out factors that might contribute to Alzheimer’s,” said Dr. Guy Caldwell, University Distinguished Research Professor.

Caldwell is co-author of a paper on the findings published in the journal Disease Models and Mechanisms. The work was supported by a Howard Hughes Medical Institute Collaborative Innovation Award.

The lead author is former UA doctoral student, Dr. Edward Griffin, now a post-doctoral researcher at the University of Alabama at Birmingham department of neurology.

Other co-authors include Dr. Kim Caldwell, UA professor of biological sciences, and Dr. Laura Berkowitz, UA lab manager and research associate. Also four other UA students were co-authors, including graduate students Samuel Scopel of St. Louis, Missouri; and Cayman Stephen of Lafayette, La.; along with undergraduate students Adam Holzhauer of Pontiac, Il.; Madeline Vaji of Cleveland, Ohio; and Ryan Tuckey of Middle Town, Maryland.

The Caldwells, along with their students, use tiny roundworms known as C. elegans, which share roughly half their genes with humans, to study human diseases. Its basic features allow inexpensive and rapid testing for a range of neurological diseases, as researchers can induce similar effects in the worm. They can be an important step in evaluating therapies in a chain of discovery from cells to animal models and, eventually, humans.

The worms have been used to study aspects of Alzheimer’s disease before, but now the UA researchers were able to show that humanized worms can be generated to emulate conditions seen in humans with genetic variation in a certain protein called Apolipoprotein E, or ApoE, for short.

“The worms recapitulate the clinical trend of Alzheimer’s risk seen in humans that harbor these heritable differences, therefore the new animal models open up the door to future mechanistic analyses and drug discovery,” Dr. Guy Caldwell said.

The exact cause of Alzheimer’s is unknown, but the effects of the disease on the brain include decreasing communication between the brain’s cells as neurons and their synapses are lost, leading to atrophy of part of the brain as the disease progresses. A person goes from short-term memory loss to dementia and eventual loss of bodily functions.

Afflicting nearly 30 million people worldwide, Alzheimer’s typically occurs in people older than 65, although early-onset Alzheimer’s does happen.

A characteristic of the disease is the folding and tangling of the protein amyloid beta into plaques as it aggregates in excessive amounts in the brain, contributing to the loss of neuron connections. This is found in nearly 70 percent of late-life Alzheimer’s.

Although the cause of amyloid beta plaques is not clear, a strong genetic risk is variation of the APOE gene. In fact, the variant, APOEε4, is found in more than 40 percent of patients. If two of the APOEε4 genes are inherited from parents, a person has a 15-fold increased risk of getting Alzheimer’s, although the chances of not getting it are still greater than a diagnosis. The presence of APOEε4 can be detected in commercial genetic tests commonly used for ancestry discovery.

During the research that led to the paper, Griffin and the team induced neurodegeneration using human amyloid beta in the worms and tested it with three variants of APOE – APOEε2, thought to provide protective measures against Alzheimer’s; APOEε3, a seemingly neutral genetic variant for the disease; and APOEε4.

“We took a worm model with amyloid beta that we previously found could already be used to discern genes and drug candidates related to Alzheimer’s, as reported in a 2011 article in Science, and now added these major genetic risk factors for the disease to it,” Caldwell said.

The UA researchers found the APOE make-up in the worm did affect neurodegeneration. In the worms, APOEε4 did not increase neurodegeneration, but the protection against it was lost. Strikingly, neurons in worms with APOEε2 were protected, as observed in humans. Worms with any APOE variant but no amyloid beta were fine.

“It’s that combination that seems to be toxic to the neurons,” Caldwell said.

APOE also affected the lifespan of the worms, with APOEε4 showing comparatively decreased survival. That’s a key to understanding Alzheimer’s as it has become more prevalent as people in developed societies live longer, Caldwell said.

“Because the worms showed distinctions in lifespan and neurodegeneration, one of the hopes going forward is that we can use these models for preclinical drug discovery,” he said. “To say that Alzheimer’s represents an unmet and urgent societal challenge is an understatement, and we need an all-hands-on-deck approach to combat it sooner.”

Researchers examining Parkinson’s resilience

More information:
Edward F. Griffin et al. ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans, Disease Models & Mechanisms (2019). DOI: 10.1242/dmm.037218

Provided by
University of Alabama in Tuscaloosa

Tiny worm mimics key genetic risk for Alzheimer’s (2019, February 19)
retrieved 20 April 2019

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles