July 12, 2016
Next Generation Alzheimer’s Disease Model
There is a new genetically engineered lab rat wit the full spectrum of brain changes associated with Alzheimer’s disease that supports the idea that increases in a molecule called beta-amyloid in the brain causes the disease. Published in the Journal of Neuroscience, the study was supported by the National Institutes of Health.
(Related: Does Alzheimer’s or Dementia Cause Hoarding?)
“We believe the rats will be an excellent, stringent pre-clinical model for testing experimental Alzheimer’s disease therapeutics,” said Terrence Town, Ph.D., the study’s senior author and a professor in the Department of Physiology & Biophysics in the Zilkha Neurogenetic Institute at the University of Southern California Keck School of Medicine, Los Angeles.
Alzheimer’s is an age-related brain disorder, affecting at least 5.1 million Americans, that gradually destroys a person’s memory, thinking and some of the most basic functionality
Pathological hallmarks of Alzheimer’s brains include abnormal levels of beta-amyloid protein that form amyloid plaques; tau proteins that clump together inside neurons and form neurofibrillary tangles; and neuron loss. In addition, glial cells — which typically support, protect, or nourish nerve cells — are overactivated in Alzheimer’s.
Plaque-forming beta-amyloid molecules are derived from amyloid precursor protein (APP). One hypothesis claims that increases in beta-amyloid initiate brain degeneration. Genetic studies on familial forms of Alzheimer’s reinforce the hypothesis by connecting the disease to mutations in APP, and to presenilin 1, a protein believed to be involved in the production beta-amyloid.
Previous studies involving rodents were only able to partially reproduce the problems caused by Alzheimer’s. To address this issue, Dr. Town and his colleagues decided to work with a certain strain of rats.
“We focused on Fischer 344 rats because their brains develop many of the age-related features seen in humans,” said Dr. Town, who conducted the study while working as a professor of Biomedical Sciences at Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California, Los Angeles.
The rats were engineered to have the mutant APP and presenilin 1 genes, which play a role in the rare, early-onset form of Alzheimer’s. Behavioral studies revealed that the rats developed both memory and learning problems with age.
“This new rat model more closely represents the brain changes that take place in humans with Alzheimer’s, including tau pathology and extensive neuronal cell death,” said Roderick Corriveau, Ph.D., a program director at NIH’s National Institute of Neurological Disorders and Stroke. “The model will help advance our understanding of the various disease pathways involved in Alzheimer’s onset and progression and assist us in testing promising interventions.”