[GRG] Tau, not amyloid-beta, triggers neuronal death


Contact: Karen Teber
Georgetown University Medical Center

Tau, not amyloid-beta, triggers neuronal death process in

WASHINGTON — New research points to tau, not amyloid-beta (Abeta)
plaque, as the seminal event that spurs neuron death in disorders
such as Alzheimer’s disease. The finding, which dramatically alters
the prevailing theory of Alzheimer’s development, also explains why
some people with plaque build-up in their brains don’t have

The study is published online today in the journal Molecular

Neuronal death happens when tau, found inside neurons, fails to
function. Tau’s role is to provide a structure — like a train track
—inside brain neurons that allows the cells to clear accumulation
of unwanted and toxic proteins.

“When tau is abnormal, these proteins, which include Abeta,
accumulate inside the neurons,” explains the study’s senior
investigator, Charbel E-H Moussa, MB, PhD, assistant professor of
neuroscience at Georgetown University Medical Center. “The cells
start to spit the proteins out, as best they can, into the
extracellular space so that they cannot exert their toxic effects
inside the cell. Because Abeta is ‘sticky,’ it clumps together into
plaque,” Moussa says.

He says his study suggests the remaining Abeta inside the neuron
(that isn’t pushed out) destroys the cells, not the plaques that
build up outside. “When tau does not function, the cell cannot
remove the garbage, which at that point includes Abeta as well as
tangles of nonfunctioning tau, and the cell dies. The Abeta
released from the dead neuron then sticks to the plaque that had
been forming.”

Moussa’s experiments in animal models also show less plaques
accumulate outside the cell when tau is functioning; when tau was
reintroduced into neurons that did not have it, plaques did not

Malfunctioning tau can occur due to errant genes or through aging.
As individuals grow older, some tau can malfunction while enough
normal tau remains to help clear the garbage. In these cases, the
neurons don’t die, he says. “That explains the confusing clinical
observations of older people who have plaque build-up, but no
dementia,” Moussa says.

Moussa has long sought a way to force neurons to clean up their
garbage. In this study, he shows that nilotinib, a drug approved to
treat cancer, can aid in that process. Nilotinib helps the neuron
clear garbage, but requires some functional tau, he says.

“This drug can work if there is a higher percentage of good to bad
tau in the cell,” Moussa says. “There are many diseases of dementia
that have malfunctioning tau and no plaque accumulation, such as
frontal temporal dementia linked to Parkinsonism,” Moussa says.
“The common culprit is tau, so a drug that helps tau do its job may
help protect against progression of these diseases.”


Co-authors include researchers from Capital Medical University in
Beijing, China, and Merck Research Laboratories.

Funding for these studies was provided by Georgetown University
grants and by Merck & Co.

Moussa is an inventor on a Georgetown University patent application
for use of nilotinib as a therapeutic approach in neurodegenerative

About Georgetown University Medical Center

Georgetown University Medical Center (GUMC) is an internationally
recognized academic medical center with a three-part mission of
research, teaching and patient care (through MedStar Health).
GUMC’s mission is carried out with a strong emphasis on public
service and a dedication to the Catholic, Jesuit principle of cura
personalis — or “care of the whole person.” The Medical Center
includes the School of Medicine and the School of Nursing & Health
Studies, both nationally ranked; Georgetown Lombardi Comprehensive
Cancer Center, designated as a comprehensive cancer center by the
National Cancer Institute; and the Biomedical Graduate Research
Organization, which accounts for the majority of externally funded
research at GUMC including a Clinical and Translational Science
Award from the National Institutes of Health.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse biological aging and age related decline for more years of healthy living. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Aging Intervention Foundation (dba for Carl I. Bourhenne Medical Research Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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