Study Measures Changes In Brain Proteins In Alzheimer’s Patients For First Time
April Flowers for redOrbit.com – Your Universe Online
A significant and potentially pivotal difference between the brains of patients with an inherited form of Alzheimer’s disease and healthy family members who do not have it has been measured by researchers at Washington University School of Medicine in St. Louis.
Researchers have long known that a protein fragment called amyloid beta builds up into plaques in Alzheimer´s patient´s brains. The theory is that these plaques cause the memory loss and other cognitive problems that characterize the disease. Different forms of amyloid beta are produced in normal brain metabolism. The new study, published in Science Translational Medicine, reveals that study participants with genetic mutations known to cause early-onset Alzheimer´s make about 20 percent more of a specific form of amyloid beta called amyloid beta 42 than family members who do not have the mutation.
The research team found another difference linked to amyloid beta 42 in the mutation carriers as well. They observed signs that amyloid beta 42 is released from the cerebrospinal fluid much more quickly than other forms of amyloid beta, possibly because amyloid beta 42 is being deposited on brain amyloid plaques.
“These results indicate how much we should target amyloid beta 42 with Alzheimer’s drugs,” said Randall Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. “We are hopeful that this and other research will lead to preventive therapies to delay or even possibly prevent Alzheimer’s disease.”
Investigating these conditions has helped researchers to develop treatments for inherited Alzheimer´s as well as laying the groundwork for advances in treatment of the much more common sporadic forms of the disease.
A majority of the amyloid beta found in the cerebrospinal fluid can be accounted for by three forms of the protein: amyloid beta 38, 40 and 42. Previous postmortem brain studies and animal research suggests that amyloid beta 42 was the most important contributor to Alzheimer’s. The findings of the current study confirm this connection and quantify the overproduction of amyloid beta 42 for the first time in living brains.
A technique that measures the rate at which amyloid beta is produced and cleared from the cerebrospinal fluid was co-developed by Bateman, who put together the team of University of Washington colleagues to see if they could develop a way to analyze the types of amyloid beta being produced in the brain.
The team, which included metabolism expert Bruce Patterson, PhD, and biomedical engineer Donald Elbert, PhD, developed a new mathematical model to describe the production and clearance of amyloid beta. The model was applied to data from 11 participants with Alzheimer´s mutations and 12 related family members without the mutations. The researchers used the model to compare the production rates of the protein’s different forms, revealing an increase in amyloid beta 42 production in subjects with an Alzheimer’s gene.
“Working in isolation, any one of us would likely have gotten the wrong answer, or no answer,” Elbert said. “Bringing our different skill sets together let us tackle a very complex physiological problem.”
The model is now being tested on data from approximately 100 Alzheimer´s patients.
“We hope that our new insights about the production and clearance of amyloid beta proteins will pave the way for future studies aimed at understanding and altering the metabolic processes that underlie this devastating disease,” Patterson said.