June 1, 2001
Alzheimer's Disease Meets its Boxing Match
Molecular Link between Alzheimer's and "Punch Drunk" Syndrome Found
(Philadelphia, PA) - In the fight to link brain
injuries and Alzheimer's Disease (AD) in humans, researchers at the University
of Pennsylvania Medical Center have found a strong contender in the molecular
weight category. Abnormal tau proteins, which form fibrous tangles in the brains
of AD sufferers, are identical to the abnormal tau proteins found in patients
with Dementia Pugilistica (DP), a memory disorder also known as Punch Drunk
- or Boxer's - Syndrome.
Researchers from Penn's Center for Neurodegenerative Disease Research (CNDR)
compared the brains of people with a genetic history of AD and the brains of
DP sufferers to discover if there is a molecular basis in humans for the notion
that brain injuries could predispose a person to AD. Their findings, published
in the June issue of the international neurology journal Acta Neuropathologica,
suggest that lesions in the two disorders arise through similar means.
"Our findings suggest that brain injury can cause Boxer's Syndrome by activating
mechanisms like the ones that cause tau lesions in Alzheimer's,' said M. Luise
Schmidt, PhD, a senior research investigator at the CNDR. "By extension,
it also suggests that a head injury can increase susceptibility to Alzheimer's
later in life."
Tau lesions, which form as fibrous clumps of abnormal tau protein amass, are
one part of the assortment of problems that characterize AD. The human brain
produces six forms of tau protein, which researchers believe have a role in
forming the network of microtubules that serve as a kind of transport system
within brain cells.
Alzheimer's Disease and Dementia Pugilistica are both part of a subset of brain
diseases known as tauopathies, and are both marked by similar physical and memory
disorders. That does not mean, however, that the diseases are the same. Although
they share the pathology, the fibrous lesions in AD and DP are generally found
in different parts of the brain.
"These findings lead us to believe that the events of brain injury lead
to the same sort of biochemical effects that cause the tau lesions in Alzheimer's,"
said John Q. Trojanowski, MD, PhD, co-director of the CNDR and professor in
the Department of Pathology and Laboratory Medicine in Penn's School of Medicine.
"The abnormal tau proteins found in people with Boxer's Syndrome are indistinguishable
from those found in patients with a familial history of Alzheimer's, and we
are exploring how they got that way."
The researchers believe that, by understanding the similarities in the diseases,
they can find the common roots. In this article, they compared the brains of
people who had a post mortem diagnosis of an inherited from of AD with the brains
of deceased ex-boxers who had a diagnosis of DP. The findings - that they share
pathology in humans - will further clarify the relationship of DP and AD as
well as other tauopathies.
The researchers also stress the need for care and protection of the brain, especially
in sporting activities. Boxers, of course, participate in a sport that exposes
them to repeated acts of brain trauma. Even those who seem fine after a traumatic
event may not realize the injury's full impact until years later. "The
effects of these self inflicted brain injuries are not always readily apparent,
and we are only beginning to understand the long-term secondary effects of the
trauma," comments Tracy K. McIntosh, PhD, director of Penn's Head Injury
Center. "It also goes to show that people have an unfortunate tendency
to willingly replicate a natural disorder."
Vicki Zhukareva, PhD, and Virginia M.-Y. Lee, PhD, of the Center of Neurodegenerative
Disease Research also contributed to the finding presented in this paper. Kathy
Lynn Newell, MD, of the Harvard Medical School, furnished the brain samples
of ex-boxers with Dementia Pugilistica. Funding for this research was provided
by the National Institutes on Aging of the National Institutes of Health.
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Founded in 1991, the Center for Neurogenerative Disease Research (CNDR) is
devoted to developing better diagnostic strategies and effective new therapies
- and encouraging the rapid translation of progress at the lab bench to the
bedside. John Q. Trojanowski, MD, PhD, and Virginia M.-Y. Lee, PhD co-direct
the Center, leading a team of over 35 Penn researchers. Based in the Department
of Pathology and Laboratory, the CNDR serves as multidisciplinary research hub
connecting researchers throughout Penn Health System. CNDR researchers pursue
a comprehensive array of research activities that extend from studies in test-tubes
or cell-culture systems to those involving animal models of neurodegenerative
diseases as well as to patient-based clinical and basic research studies.