Bret Stetka, MD; José G. Merino, MD, MPhil


May 07, 2012

Editor's Note:

At the 2012 Annual Meeting of the American Academy of Neurology (AAN) in New Orleans, Louisiana, Medscape sat down with José G. Merino, MD, MPhil, to discuss 4 intriguing areas of research presented at the meeting. Dr. Merino is a neurologist at Johns Hopkins Community Physicians in Bethesda, Maryland; a member of the AAN Science Committee; and moderator of this year's AAN Hot Topics session.

Tau Gets Tricky

Medscape: How does the AAN Science Committee decide which presentations to include in the Hot Topics session?

Dr. Merino: The committee is made up of approximately 20 members of the AAN, typically academic researchers and leaders in their field. We get together multiple times a year and plan the scientific activities for the meeting. The idea of the Hot Topics session is to highlight important work that may have been presented at other conferences, often neuroscience meetings, but that we think may be of interest to AAN members. Because the speakers are working on research that is novel, this session gives neurologists a glimpse into what's coming in terms of the science that may affect practice a few years down the road.

Medscape: The first Hot Topic was presented by Dr. Karen Duff of Columbia University. Can you briefly summarize Dr. Duff's work?

Dr. Merino: Dr. Duff is Professor of Pathology at Columbia University, She focuses on the mechanisms involved in the development of neurodegenerative diseases and the development of new therapies based on her findings. One of her current areas of interest is the development of neurofibrillary tangles. These tangles are made up of abnormally phosphorylated tau. In initial stages of Alzheimer disease, these tangles are seen only in the hippocampus, but later on they can be seen throughout the brain. Dr. Duff is using a mouse model to determine whether these tangles develop independently from the hippocampal pathology or whether the tauopathy spreads from neuron to neuron.

Medscape: Meaning that the tau protein literally jumps from neuron to neuron, or more that the pathology causing the production of tau tangles somehow impairs neighboring neurons which then produce their own tau?

Dr. Merino: Her data show that the pathology spreads across synapses along anatomically connected networks, rather than as a result of independent events in vulnerable regions. The mechanism for how this happens is not yet known. This is potentially very important because it may give us insight into how markers of neuronal damage in one area of the brain migrate into other areas. Once Dr. Duff identifies the mechanism of why this happens, she could go on to investigate therapies acting on this mechanism.

Sex Differences in Alzheimer Disease?

Medscape: Can you discuss Dr. Diaz Brinton's presentation?

Dr. Merino: Yes. Dr. Roberta Diaz Brinton is Chair in Therapeutic Discovery and Development and Professor of Pharmacology and Pharmaceutical Science, Biomedical Engineering and Neurology, at the University of Southern California. She also directs the USC Star Science Education Program and the Center for Scientific Translation at the USC Clinical and Translational Science Institute. Her work has focused on age- and sex-associated mechanisms of neurodegeneration, specifically how there are sex differences in bioenergetic requirements and how neurons age in the brain. Women are more likely than men to have Alzheimer disease. This may be partly due to women living longer, but Dr. Diaz Brinton thinks that hormonal factors are at play. She has shown that estrogen regulates mitochondrial function, and that mitochondrial dysfunction, particularly in the perimenopausal period, may play a role in neurodegeneration. These findings are very important because they open up a therapeutic opportunity to prevent the development, or to slow down the progress, of Alzheimer disease.

Medscape: So, one day we might have gender-specific therapies for Alzheimer disease?

Dr. Merino: Her work suggests that there may be a benefit to the use of estrogen in the perimenopausal period, when the brain is still healthy, to reduce the risk for neurodegenerative conditions like Alzheimer or Parkinson disease.


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