Neuroscience 2014 Coverage
This research was supported by BrightFocus
Society for Neuroscience meeting in Washington, DC, this week. Two close colleagues of BrightFocus took part in press conferences to explain new directions in Alzheimer’s research.
Cynthia Lemere, PhD, a member of the BrightFocus Scientific Review Committee, was part of a panel on detecting and preventing neuroinflammation as a factor contributing to Alzheimer’s. She is a researcher and associate professor of neurology at Harvard’s Brigham and Women’s Hospital.
As background, the human brain consists primarily of neurons, which transmit signals, and non-neuronal cells, called “glia,” that are there to nourish and protect neurons. Already, the blood-brain barrier defends the brain against entry of pathogens and toxic substances, but beyond that, a subcategory of glia, called “microglia,” are the first line of active immune defense against unwanted intruders. Like an occupying force, their job is to constantly sweep the neuronal terrain for signs of danger, including plaques, damaged neurons, and infectious agents. The microglia remove these threats mostly remove by ingesting them (a process known as phagocytosis).
Even in healthy people, microglia levels naturally increase with aging. Microglia also increase in the presence of early plaques and neuronal damage associated with preclinical Alzheimer’s. This in turn seems to trigger downstream changes, like inflammation, that hasten the disease.
Currently there is no FDA-approved technology for imaging neuroinflammatory factors. In people known to be at risk for Alzheimer’s disease, such imaging might be useful as a “biomarker” or early warning of the disease, and it could possibly help determine when treatment should begin.
Lemere discussed the results of a study funded by GE Healthcare that uses its PET scan technology with a new tracing agent to track the spread and worsening of these inflammatory factors. She is senior author on the SfN abstract by Bob Liu, PhD, et al, showing that in mice engineered with Alzheimer’s disease, the tracer was successful in showing more microglial activity in the cortex and hippocampal regions involved with memory.
Whereas the definitive diagnosis of Alzheimer’s disease traditionally occurs postmortem, after pathologists have had a chance to examine a person’s brain, “we now have a new tool,” Lemere remarked, and “with these new PET tracers, it’s possible to get more insights into Alzheimer’s disease in the living.”
GE Healthcare is expected to seek FDA approval for the new technology.
Surprising News About Tau Turnover--An SfN ‘Hot Topic’
Another member of the BrightFocus Scientific Review Committee, David Holtzman, MD, of Washington University in St. Louis, had his study differentiated from thousands at SfN as an SfN “hot topic.”
Holtzman is senior author on the abstract by Kaoru Yamada, PhD, (first author) of the University of Tokyo, and other colleagues worldwide. It describes their investigation into tau protein clearance in the brain. Their results were presented at an SfN scientific session (SfN Program No. 578.02).
Tau, these researchers note, is a normally soluble protein that becomes insoluble and accumulates in its diseased state. In the healthy brain, there’s a balance between tau production and clearance to maintain normal levels. It’s been hypothesized that impaired tau clearance may be one of the mechanisms behind the accumulation of misfolded tau, contributing to Alzheimer’s disease. However, tau “turnover” in the living brain has not been well studied.
After investigating tau clearance in living mice, these investigators found that even normal tau protein has a relatively long half-life of 10-11 days (as compared with 1-2 hours for Aβ peptide) and does not disappear as quickly from the brain as expected. For most abnormal forms of tau, the rate of clearance is longer, but varies. Their results have led them to speculate that, for different forms of tau, different clearance mechanisms are involved. It also supports the hypothesis that inefficient clearance of particular forms of tau might lead to tau tangles. These researchers speculate that improving clearance of the slowest-clearing, more insoluble forms of tau could become a therapeutic strategy against Alzheimer’s.
Neurons are the core components of the brain and spinal cord of the central nervous system (CNS) that process and transmit information.
Evidence points to beta amyloid (Aβ) peptide accumulation as a culprit in preclinical Alzheimer’s disease.
The cerebral cortex is the outer layer of brain tissue, and is responsible for many "higher-order" functions like language and information processing.
The hippocampus is a part of the brain that plays a significant role in the formation of long-term memories. The plural of hippocampus is hippocampi.
One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.
The neurofibrillary tangles found in Alzheimer's disease consist primarily of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. In Alzheimer's disease, however, the tau protein is abnormal and the microtubule structures collapse. Abnormal tau formations, known as “tauopathy,” have been associated with a number of neurodegenerative disorders.