ALS Drug May Reverse Some Age-Related Cognitive Decline Interview with:
Ana Pereira, MD
Instructor in Clinical Medicine

Bruce McEwen’s laboratory
Rockefeller University What is the background for this study?

Dr. Pereira: The neurons most susceptible to dying in Alzheimer’s disease are the ones that use glutamate as a neurotransmitter (chemical messengers that enable neurotransmission). Glutamate is the major excitatory neurotransmitter in the brain and its regulation is critical for learning and memory.

When glutamate is not located in the correct place and amount, it causes several deleterious effects to neurons that can ultimately lead to cell death. Importantly, the glutamate transporter EAAT2 is the dominant regulator of glutamate levels and it is highly depressed in Alzheimer’s disease. Furthermore, glutamatergic dysregulation is implicated in several pathological mechanisms in Alzheimer’s disease including the release and toxicities of the proteins implicated in Alzheimer’s disease: amyloid-beta (which form amyloid plaques) and tau (which form neurofibrillary tangles).

Better regulation of glutamatergic neural circuits is critically important to effectively treat age-related cognitive decline and Alzheimer’s disease. What should readers take away from your report?

Dr. Pereira: The essence is we used a drug known to modulate glutamate, riluzole, currently approved for ALS, and when we gave it to old rats, we saw it reversed many of the changes that begin in middle age in the hippocampus. We saw a similar pattern when we compared the riluzole-induced changes to data from Alzheimer’s patients—in a number of key pathways in the hippocampus, the drug produced an effect opposing that of the disease.  We found that in addition to recovering the expression of the glutamate transporter EAAT2, the drug restored genes critical for neural communication and plasticity, both of which decline with aging and even more significantly with Alzheimer’s disease.

These studies further implicate glutamatergic targets for development of novel treatments for age-related cognitive decline and Alzheimer’s disease and in particular, recovery of activity of glutamate transporters that are critically important for physiological function of excitatory synapses. Is there anything else you would like to add?

Dr. Ana Pereira is leading an ongoing pilot clinical trial at the Rockefeller University with RILUZOLE in mild Alzheimer’s disease patients. For interested participants, please call 1800-RUCARES. Thank you for your contribution to the community.


Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on

A C Pereira, J D Gray, J F Kogan, R L Davidson, T G Rubin, M Okamoto, J H Morrison, B S McEwen. Age and Alzheimer’s disease gene expression profiles reversed by the glutamate modulator riluzole.

Molecular Psychiatry, 2016; DOI: 10.1038/mp.2016.33

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