June 1, 2001
Alzheimer's Disease Meets its Boxing
Match
Molecular Link between Alzheimer's and "Punch
Drunk" Syndrome Found in Humans
(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.
# # #
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.
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