Here is a good example of what I"ve posted here many times, namely,
that the underlying cause of various "chronic diseases" is directly
or indirectly related to free radical damage in one form or another.
Notice that this (i.e., free radical damage/oxidative stress) is not
even mentioned in the report, yet it took me about a minute to find an
abstract that makes the case for oxidative stress as the cause.  The
researchers discussed and quoted in the report make it seem like there
is some sort of mystery involved, when there is none.  They make it
seem as though prevention is not possible.  There is no denying that
free radical damage can be prevented, though the exact foods and
supplements to consume is not totally clear, which is why that is where
the research money should be spent.  Moreover, you can avoid the highly
unsaturated fatty acid foods while eating things like berries and dark
chocolate.

These "researchers" appear to be unaware of the fact that oxidative
stress is what is causing the problem they observed further down the
"disease pathway."  They may not fully understand the significance
of oxidative stress, and that is why I am trying to educate those who
read my posts here about this point (i.e., that it's the underlying
cause but that many "scientists" don't seem to understand it or
are unaware that it appears to always be the root cause).  It's
interesting that they say a "smoking gun" has been found, but then say
that it is not the root cause.  The evidence suggests in the strongest
possible terms (I've got plenty of other abstracts that make the point)
that oxidative stress is the problem, so if there is a "smoking gun,"
it's almost certainly oxidative stress.  Is it that they can't make any
money designing drugs to combat oxidative stress, or is it that they
are ignorant?  It doesn't matter to you if you  just want to do you
best to avoid Alzheimer's Disease.  If you print this post out, you
will be able to think through this, and then tell others what is going
on, that is, too many scientists get focused on problems that do not
address the root cause, and may in fact lead to greater damage that the
original "disease" would have done (usually because of the drug's
side-effects).

8/6/2005
Smoking Gun For Alzheimer's Disease

In a world first, Australian researchers have found a toxin that plays
an important role in the progression of Alzheimer's disease (AD), the
most common cause of dementia.

The research is significant because drugs that are in the advanced
developmental phase for other conditions might be able to be used on
Alzheimer's patients, to halt the disease progressing. At present,
there are only minimally effective treatments for the condition, which
is increasing with the ageing population.

"We found that all of the brains of dementia patients showed quinolinic
acid neurotoxicity," said Professor Bruce Brew, Director of Neurology
at St Vincent's Hospital and Professor of Medicine at the University of
New South Wales (UNSW). "This acid kills nerve cells in the brain,
leading to brain dysfunction and ultimately death."

There are currently more than 200, 000 people with Alzheimer's disease
in Australia. The number will exceed 730, 000 by 2050.

"Quinolinic acid is part of a biochemical pathway called the kynurenine
pathway," said the lead author of the research, UNSW's Dr Gilles
Guillemin, who is based at the Centre for Immunology at St Vincent's
Hospital. "The activation of that pathway is also found in other major
brain diseases including Huntington's disease, stroke, dementia and
schizophrenia."

The paper Indoleamine 2, 3 dioxygenase and quinolinic acid
Immunoreactivity in Alzheimer's disease hippocampus has been published
this week in the leading international journal Neuropathology and
Applied Neurobiology. It is the result of collaboration between
researchers from St Vincent's Hospital, UNSW, the University of Sydney
and Hokkaido University, Japan.

"There are several drugs which can block this pathway, which are
already under investigation by our laboratory and others," said Dr
Guillemin.

The drugs, which would need to be tested for efficacy, could be used to
complement other treatments.

"Quinolinic acid may not be the cause of Alzheimer's disease, but it
plays a key role in its progression," said Alzheimer's researcher, Dr
Karen Cullen from the University of Sydney. "It's the smoking gun, if
you like.

"While we won't be able to prevent people from getting Alzheimer's
disease, we may eventually, with the use of drugs, be able to slow down
the progression."

The other researchers are Claire Noonan from Sydney University and
Osamu Takikawa from Hokkaido University, Japan. The research is
significant because drugs that are in the advanced developmental phase
for other conditions might be able to be used on Alzheimer's patients,
to halt the disease progressing. At present, there are only minimally
effective treatments for the condition, which is increasing with the
ageing population.

"We found that all of the brains of dementia patients showed quinolinic
acid neurotoxicity," said Professor Bruce Brew, Director of Neurology
at St Vincent's Hospital and Professor of Medicine at the University of
New South Wales (UNSW). "This acid kills nerve cells in the brain,
leading to brain dysfunction and ultimately death."

There are currently more than 200, 000 people with Alzheimer's disease
in Australia. The number will exceed 730, 000 by 2050.

"Quinolinic acid is part of a biochemical pathway called the kynurenine
pathway," said the lead author of the research, UNSW's Dr Gilles
Guillemin, who is based at the Centre for Immunology at St Vincent's
Hospital. "The activation of that pathway is also found in other major
brain diseases including Huntington's disease, stroke, dementia and
schizophrenia."

The paper Indoleamine 2, 3 dioxygenase and quinolinic acid
Immunoreactivity in Alzheimer's disease hippocampus has been published
this week in the leading international journal Neuropathology and
Applied Neurobiology. It is the result of collaboration between
researchers from St Vincent's Hospital, UNSW, the University of Sydney
and Hokkaido University, Japan.

"There are several drugs which can block this pathway, which are
already under investigation by our laboratory and others," said Dr
Guillemin.

The drugs, which would need to be tested for efficacy, could be used to
complement other treatments.

"Quinolinic acid may not be the cause of Alzheimer's disease, but it
plays a key role in its progression," said Alzheimer's researcher, Dr
Karen Cullen from the University of Sydney. "It's the smoking gun, if
you like.

"While we won't be able to prevent people from getting Alzheimer's
disease, we may eventually, with the use of drugs, be able to slow down
the progression."

The other researchers are Claire Noonan from Sydney University and
Osamu Takikawa from Hokkaido University, Japan.

Source: www.sciencedaily.com

Br J Pharmacol. 1999 Dec;128(8):1754-60.

Oxidative stress as a mechanism for quinolinic acid-induced hippocampal
damage: protection by melatonin and deprenyl.

Behan WM, McDonald M, Darlington LG, Stone TW.

Institute of Biomedical & Life Sciences, West Medical Building,
University of Glasgow, Glasgow G12 8QQ.

1. There are differences between the excitotoxic actions of quinolinic
acid and N-methyl-D-aspartate (NMDA) which suggest that quinolinic acid
may act by mechanisms additional to the activation of NMDA receptors.
The present study was designed to examine the effect of a potent
antioxidant, melatonin, and the potential neuroprotectant, deprenyl, as
inhibitors of quinolinic acid-induced brain damage. Injections were
made into the hippocampus of anaesthetized rats, which were allowed to
recover before the brains were taken for histology and the counting of
surviving neurones. 2. Quinolinic acid (120 nmols) induced damage to
the pyramidal cell layer, which was prevented by the co-administration
of melatonin (5 nmols locally plus 2x20 mg kg(-1) i.p.). This
protective effect was not prevented by the melatonin receptor blocker
luzindole. Neuronal damage produced by NMDA (120 nmols) was not
prevented by melatonin. 3. Quinolinic acid increased the formation of
lipid peroxidation products from hippocampal tissue and this effect was
prevented by melatonin. 4. Deprenyl also prevented quinolinic
acid-induced damage at a dose of 50 nmols but not 10 nmols plus 2x1.0
mg kg(-1) i.p. The non-selective monoamine oxidase inhibitor nialamide
(10 and 50 nmols plus 2x25 mg kg(-1)) did not afford protection. 5. The
results suggest that quinolinic acid-induced neuronal damage can be
prevented by a receptor-independent action of melatonin and deprenyl,
agents which can act as a potent free radical scavenger and can
increase the activity of endogenous antioxidant enzymes respectively.
This suggests that free radical formation contributes significantly to
quinolinic acid-induced damage in vivo.