peroxynitrite does NOT cause Alzheimer's Disease

[Mark Thorson]

There's a large population of people who dose themselves
with large amounts of peroxynitrite all day, every day.
These people are tobacco smokers:

http://www.researchgate.net/profile/Thomas_Mueller41/publication/14156121_Evidence_for_peroxynitrite_as_an_oxidative_stress-inducing_compound_of_aqueous_cigarette_smoke_fractions/links/00b49536011180da52000000.pdf

If peroxynitrite _causes_ Alzheimer's Disease, smoking
would be a major risk factor for AD. But studies show
it is not. If anything, tobacco smoking might be
protective:

http://www.researchgate.net/profile/Amy_Borenstein_Graves/publication/230584479_Alcohol_and_tobacco_consumption_as_risk_factors_for_Alzheimer's_disease_a_collaborative_re-analysis_of_case-control_studies/links/0deec53a5a4a677f32000000.pdf

This is not to say that peroxynitrite plays no role
in the pathogenic process of AD. I think it plays
a major role sustaining and exacerbating the disease
process after the process is initiated. But it is
not the initiating cause. If it were, tobacco smoking
would be a major risk factor for AD, and we would see
AD developing frequently in youth and middle age in
heavy smokers. We don't see either of these things.
Peroxynitrite does not cause Alzheimer's Disease.

[L***@wnc.edu]

Post by Mark Thorson
There's a large population of people who dose themselves
with large amounts of peroxynitrite all day, every day.
http://www.researchgate.net/profile/Thomas_Mueller41/publication/14156121_Evidence_for_peroxynitrite_as_an_oxidative_stress-inducing_compound_of_aqueous_cigarette_smoke_fractions/links/00b49536011180da52000000.pdf
If peroxynitrite _causes_ Alzheimer's Disease, smoking
would be a major risk factor for AD. But studies show
it is not. If anything, tobacco smoking might be
http://www.researchgate.net/profile/Amy_Borenstein_Graves/publication/230584479_Alcohol_and_tobacco_consumption_as_risk_factors_for_Alzheimer's_disease_a_collaborative_re-analysis_of_case-control_studies/links/0deec53a5a4a677f32000000.pdf
This is not to say that peroxynitrite plays no role
in the pathogenic process of AD. I think it plays
a major role sustaining and exacerbating the disease
process after the process is initiated. But it is
not the initiating cause. If it were, tobacco smoking
would be a major risk factor for AD, and we would see
AD developing frequently in youth and middle age in
heavy smokers. We don't see either of these things.
Peroxynitrite does not cause Alzheimer's Disease.

Despite some initial studies to the contrary, smoking does increase the risk for Alzheimer's disease precisely because it does increase the formation of peroxynitrites.

http://www.ncbi.nlm.nih.gov/pubmed/24924665

http://apps.who.int/iris/bitstream/10665/128041/1/WHO_NMH_PND_CIC_TKS_14.1_eng.pdf

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037043/

[Mark Thorson]

Post by L***@wnc.edu
Despite some initial studies to the contrary, smoking
does increase the risk for Alzheimer's disease precisely
because it does increase the formation of peroxynitrites.

You're making assertions unsupported by any data.
I cited the data on which we can say with a high degree
of confidence that peroxynitrite is not the cause of
Alzheimer's Disease. It may play a downstream role
in the disease process, but it does not initiate the
disease process.

Post by L***@wnc.edu
http://www.ncbi.nlm.nih.gov/pubmed/24924665

This is a review article and a study of MRI imaging
of the brains of cognitively normal people using the
amyloid beta tracer florbetapir which found higher
retention of florbetapir in the brains of smokers and
former smokers. This isn't a study which shows smoking
increases the risk of AD because none of these people
had AD. We don't know the cause of this retention
(for example, whether it was caused by peroxynitrite)
nor whether it will eventually show an increased
risk of AD.

Post by L***@wnc.edu
http://apps.who.int/iris/bitstream/10665/128041/1/WHO_NMH_PND_CIC_TKS_14.1_eng.pdf

There's no new data here which contradicts the studies
which show smoking does not increase the risk of AD
(and may even be protective) because there's no new
data here at all. This is a review article, not a
study nor a meta-analysis.

Post by L***@wnc.edu
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037043/

There's no new data here either. This is another
review article, not a study nor a meta-analysis.

You have failed to cite any new data which contradicts
the existing data against the notion that peroxynitrite
causes AD. The case against this notion rests on data
that shows a) smokers expose themselves to high levels
of peroxynitrite and b) smoking does not increase the
risk of AD and may even reduce it. Certainly, if
peroxynitrite were the actual cause of AD, we'd see
a profound increase in the risk of AD from smoking.
We do not see this increase.

[Mark Thorson]

Post by Mark Thorson
This is a review article and a study of MRI imaging
of the brains of cognitively normal people using the
amyloid beta tracer florbetapir which found higher
retention of florbetapir in the brains of smokers and

Correction, florbetapir is a PET scan imaging agent,
not MRI.

[L***@wnc.edu]

Post by Mark Thorson

Post by Mark Thorson
This is a review article and a study of MRI imaging
of the brains of cognitively normal people using the
amyloid beta tracer florbetapir which found higher
retention of florbetapir in the brains of smokers and

Correction, florbetapir is a PET scan imaging agent,
not MRI.

If you are resting your case against peroxynitrites as a cause of Alzheimer's disease on the basis that smoking does not increase the risk for Alzheimer's disease, it is a very flimsy case:

A recent study, sponsored by Kaiser Permanente and published in the Archives of Internal Medicine, has found that smoking increases elevates the risk of Alzheimer's disease and vascular dementia. An analysis of more than 20,000 men and women found a 157% heightened risk of Alzheimer's disease in people who had smoked more than two packs of cigarettes a day.

[Mark Thorson]

Post by L***@wnc.edu
If you are resting your case against peroxynitrites
as a cause of Alzheimer's disease on the basis that
smoking does not increase the risk for Alzheimer's
A recent study, sponsored by Kaiser Permanente and
published in the Archives of Internal Medicine, has
found that smoking increases elevates the risk of
Alzheimer's disease and vascular dementia. An analysis
of more than 20,000 men and women found a 157%
heightened risk of Alzheimer's disease in people
who had smoked more than two packs of cigarettes a day.

Where's the study? Who's the author? Does it exist?

[L***@wnc.edu]

Post by Mark Thorson

Post by L***@wnc.edu
If you are resting your case against peroxynitrites
as a cause of Alzheimer's disease on the basis that
smoking does not increase the risk for Alzheimer's
A recent study, sponsored by Kaiser Permanente and
published in the Archives of Internal Medicine, has
found that smoking increases elevates the risk of
Alzheimer's disease and vascular dementia. An analysis
of more than 20,000 men and women found a 157%
heightened risk of Alzheimer's disease in people
who had smoked more than two packs of cigarettes a day.

Where's the study? Who's the author? Does it exist?

The answers to your questions.

http://share.kaiserpermanente.org/article/heavy-smoking-doubles-alzheimers-disease-dementia-risk/

[Mark Thorson]

Post by L***@wnc.edu

Post by Mark Thorson

Post by L***@wnc.edu
If you are resting your case against peroxynitrites
as a cause of Alzheimer's disease on the basis that
smoking does not increase the risk for Alzheimer's
A recent study, sponsored by Kaiser Permanente and
published in the Archives of Internal Medicine, has
found that smoking increases elevates the risk of
Alzheimer's disease and vascular dementia. An analysis
of more than 20,000 men and women found a 157%
heightened risk of Alzheimer's disease in people
who had smoked more than two packs of cigarettes a day.

Where's the study? Who's the author? Does it exist?

The answers to your questions.
http://share.kaiserpermanente.org/article/heavy-smoking-doubles-alzheimers-disease-dementia-risk/

If you look at the actual study (rather than the press release)
you'll see that for light smokers, there is a strong protective
effect against AD. Referring to Table 2 of the study, they have
85% of the risk of developing AD as compared to nonsmokers.
Moderate smokers (0.5 to 1 pack/day) have a slightly increased
risk, 109% of the risk of nonsmokers. 1 to 2 pack/day smokers
have 117% of the risk.

You only see the big jump in risk for the heavy smokers, 236%.
But there's a flaw in this statistic. The total study population
is 33,108. How many heavy smokers developed AD in this study?
Only 17. This result is statistical noise. This study does
not demonstrate a strong increase in risk of developing AD from
smoking, which would be expected if peroxynitrite causes AD.

Once again Lane, you are just blowing smoke. You have latched
on to your pet theory, and there's no amount of scientific data
that will change your mind.

[Lane]

Post by Mark Thorson

Post by L***@wnc.edu

Post by Mark Thorson

Post by L***@wnc.edu
If you are resting your case against peroxynitrites
as a cause of Alzheimer's disease on the basis that
smoking does not increase the risk for Alzheimer's
A recent study, sponsored by Kaiser Permanente and
published in the Archives of Internal Medicine, has
found that smoking increases elevates the risk of
Alzheimer's disease and vascular dementia. An analysis
of more than 20,000 men and women found a 157%
heightened risk of Alzheimer's disease in people
who had smoked more than two packs of cigarettes a day.

Where's the study? Who's the author? Does it exist?

The answers to your questions.
http://share.kaiserpermanente.org/article/heavy-smoking-doubles-alzheimers-disease-dementia-risk/

If you look at the actual study (rather than the press release)
you'll see that for light smokers, there is a strong protective
effect against AD. Referring to Table 2 of the study, they have
85% of the risk of developing AD as compared to nonsmokers.
Moderate smokers (0.5 to 1 pack/day) have a slightly increased
risk, 109% of the risk of nonsmokers. 1 to 2 pack/day smokers
have 117% of the risk.
You only see the big jump in risk for the heavy smokers, 236%.
But there's a flaw in this statistic. The total study population
is 33,108. How many heavy smokers developed AD in this study?
Only 17. This result is statistical noise. This study does
not demonstrate a strong increase in risk of developing AD from
smoking, which would be expected if peroxynitrite causes AD.
Once again Lane, you are just blowing smoke. You have latched
on to your pet theory, and there's no amount of scientific data
that will change your mind.

Good quality evidence would make me change my mind, but you have made a general assertion not supported by the evidence: namely that peroxynitrites cannot be the cause of Alzheimer's disease because smoking does not increase the risk for Alzheimer's disease and that it might actually be protective. The study did indicate that light smoking slightly decreases the risk for Alzheimer's disease (although it slightly increases the risk for vascular dementia). Many of the compounds in tobacco increase peroxynitrite levels, but some of the phenolic compounds which escape oxidation may actually scavenge peroxynitrites in the brain (hydroquinones, for instance).

Heavy smoking increases peroxynitrite levels and the risk for Alzheimer's disease (that there were only 17 in the study reflects the earlier mortality rates among heavy smokers). This of course does not prove that peroxynitrites cause Alzheimer's disease, but your line of argument does not prove the opposite.

The link through the press release reverted back to the general journal so here is the link to the actual article for anyone who wants to read it.

http://archinte.jamanetwork.com/article.aspx?articleid=226695

[L***@wnc.edu]

Post by Lane

Post by Mark Thorson

Post by L***@wnc.edu

Post by Mark Thorson

Post by L***@wnc.edu
If you are resting your case against peroxynitrites
as a cause of Alzheimer's disease on the basis that
smoking does not increase the risk for Alzheimer's
A recent study, sponsored by Kaiser Permanente and
published in the Archives of Internal Medicine, has
found that smoking increases elevates the risk of
Alzheimer's disease and vascular dementia. An analysis
of more than 20,000 men and women found a 157%
heightened risk of Alzheimer's disease in people
who had smoked more than two packs of cigarettes a day.

Where's the study? Who's the author? Does it exist?

The answers to your questions.
http://share.kaiserpermanente.org/article/heavy-smoking-doubles-alzheimers-disease-dementia-risk/

If you look at the actual study (rather than the press release)
you'll see that for light smokers, there is a strong protective
effect against AD. Referring to Table 2 of the study, they have
85% of the risk of developing AD as compared to nonsmokers.
Moderate smokers (0.5 to 1 pack/day) have a slightly increased
risk, 109% of the risk of nonsmokers. 1 to 2 pack/day smokers
have 117% of the risk.
You only see the big jump in risk for the heavy smokers, 236%.
But there's a flaw in this statistic. The total study population
is 33,108. How many heavy smokers developed AD in this study?
Only 17. This result is statistical noise. This study does
not demonstrate a strong increase in risk of developing AD from
smoking, which would be expected if peroxynitrite causes AD.
Once again Lane, you are just blowing smoke. You have latched
on to your pet theory, and there's no amount of scientific data
that will change your mind.

Good quality evidence would make me change my mind, but you have made a general assertion not supported by the evidence: namely that peroxynitrites cannot be the cause of Alzheimer's disease because smoking does not increase the risk for Alzheimer's disease and that it might actually be protective. The study did indicate that light smoking slightly decreases the risk for Alzheimer's disease (although it slightly increases the risk for vascular dementia). Many of the compounds in tobacco increase peroxynitrite levels, but some of the phenolic compounds which escape oxidation may actually scavenge peroxynitrites in the brain (hydroquinones, for instance).
Heavy smoking increases peroxynitrite levels and the risk for Alzheimer's disease (that there were only 17 in the study reflects the earlier mortality rates among heavy smokers). This of course does not prove that peroxynitrites cause Alzheimer's disease, but your line of argument does not prove the opposite.
The link through the press release reverted back to the general journal so here is the link to the actual article for anyone who wants to read it.
http://archinte.jamanetwork.com/article.aspx?articleid=226695

Another study that produced similar results to the Kaiser study. The risk for Alzheimer's disease depends on the amount of smoking; whereas light smoking decreases the risk for Alzheimer's disease; medium to heavy smoking increases the risk for Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/15061830

I don't like mouse models for Alzheimer's disease because they are misleading, especially since the level of oxidative stress in mice designed to have Alzheimer's disease is less than in humans with the disease. The findings for this study suggesting a link between (passive) smoking, oxidative stress, and an increased risk for Alzheimer's disease may have merit, though.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036752

[Mark Thorson]

Post by Lane
Good quality evidence would make me change my mind,
but you have made a general assertion not supported
by the evidence: namely that peroxynitrites cannot
be the cause of Alzheimer's disease because smoking
does not increase the risk for Alzheimer's disease
and that it might actually be protective. The study
did indicate that light smoking slightly decreases
the risk for Alzheimer's disease (although it
slightly increases the risk for vascular dementia).
Many of the compounds in tobacco increase
peroxynitrite levels, but some of the phenolic
compounds which escape oxidation may actually
scavenge peroxynitrites in the brain (hydroquinones,
for instance).

If the protective effect came from other components
of cigarette smoke, the study I linked to earlier
would not have found peroxynitrites in cells exposed
to cigarette smoke.

http://www.researchgate.net/profile/Thomas_Mueller41/publication/14156121_Evidence_for_peroxynitrite_as_an_oxidative_stress-inducing_compound_of_aqueous_cigarette_smoke_fractions/links/00b49536011180da52000000.pdf

Post by Lane
Heavy smoking increases peroxynitrite levels and
the risk for Alzheimer's disease (that there were
only 17 in the study reflects the earlier mortality
rates among heavy smokers). This of course does not
prove that peroxynitrites cause Alzheimer's disease,
but your line of argument does not prove the opposite.

If peroxynitrite were the cause of AD, we'd see much
greater risk in people who chronically dose themselves
with peroxynitrite. Medical ethics wouldn't allow us
to do this directly, but smokers provide a convenient
study population who already do. And they are not at
increased risk for AD. Your study only found increased
risk at the highest dose level, above 2 packs a day.
Not at 2 packs, only above 2 packs. If you're smoking
3 packs a day or more, you've got serious problems just
from that. There has been speculation that hypoxia
may cause AD, and if you're smoking 3 or 4 packs you'll
have a little hypoxia just from the carbon monoxide
exposure reducing the oxygen carrying capacity of your
blood. Not to mention COPD and other impairments to
getting oxygen into the brain.

There are multiple large studies in people, not rodents,
showing either a protective effect or no effect on AD
from smoking, summarized in this meta-analysis.

http://www.researchgate.net/profile/Amy_Borenstein_Graves/publication/230584479_Alcohol_and_tobacco_consumption_as_risk_factors_for_Alzheimer's_disease_a_collaborative_re-analysis_of_case-control_studies/links/0deec53a5a4a677f32000000.pdf

When you ignore data that refutes your pet theory,
you cross the line into crackpottery.

[L***@wnc.edu]

Post by Mark Thorson

Post by Lane
Good quality evidence would make me change my mind,
but you have made a general assertion not supported
by the evidence: namely that peroxynitrites cannot
be the cause of Alzheimer's disease because smoking
does not increase the risk for Alzheimer's disease
and that it might actually be protective. The study
did indicate that light smoking slightly decreases
the risk for Alzheimer's disease (although it
slightly increases the risk for vascular dementia).
Many of the compounds in tobacco increase
peroxynitrite levels, but some of the phenolic
compounds which escape oxidation may actually
scavenge peroxynitrites in the brain (hydroquinones,
for instance).

If the protective effect came from other components
of cigarette smoke, the study I linked to earlier
would not have found peroxynitrites in cells exposed
to cigarette smoke.
http://www.researchgate.net/profile/Thomas_Mueller41/publication/14156121_Evidence_for_peroxynitrite_as_an_oxidative_stress-inducing_compound_of_aqueous_cigarette_smoke_fractions/links/00b49536011180da52000000.pdf

Post by Lane
Heavy smoking increases peroxynitrite levels and
the risk for Alzheimer's disease (that there were
only 17 in the study reflects the earlier mortality
rates among heavy smokers). This of course does not
prove that peroxynitrites cause Alzheimer's disease,
but your line of argument does not prove the opposite.

If peroxynitrite were the cause of AD, we'd see much
greater risk in people who chronically dose themselves
with peroxynitrite. Medical ethics wouldn't allow us
to do this directly, but smokers provide a convenient
study population who already do. And they are not at
increased risk for AD. Your study only found increased
risk at the highest dose level, above 2 packs a day.
Not at 2 packs, only above 2 packs. If you're smoking
3 packs a day or more, you've got serious problems just
from that. There has been speculation that hypoxia
may cause AD, and if you're smoking 3 or 4 packs you'll
have a little hypoxia just from the carbon monoxide
exposure reducing the oxygen carrying capacity of your
blood. Not to mention COPD and other impairments to
getting oxygen into the brain.
There are multiple large studies in people, not rodents,
showing either a protective effect or no effect on AD
from smoking, summarized in this meta-analysis.
http://www.researchgate.net/profile/Amy_Borenstein_Graves/publication/230584479_Alcohol_and_tobacco_consumption_as_risk_factors_for_Alzheimer's_disease_a_collaborative_re-analysis_of_case-control_studies/links/0deec53a5a4a677f32000000.pdf
When you ignore data that refutes your pet theory,
you cross the line into crackpottery.

First of all, it is not a matter of no peroxynitrite damage to the brain it is a matter of less peroxynitrite damage to the brain in light smokers versus moderate to heavy smokers. Secondly most heavy smokers don't live long enough to get Alzheimer's disease. If they did, the risk figure would likely be considerably higher.

You have now ignored two studies showing that medium to heavy cigarette use increases the risk for Alzheimer's disease. Certainly it can also increase the risk for vascular dementia and stroke. I will put the conclusions for both studies up for you.

Kaiser study: To our knowledge, this is the first study evaluating the amount of midlife smoking on long-term risk of dementia and dementia subtypes in a large multiethnic cohort. Our study suggests that heavy smoking in middle age increases the risk of both AD and VaD for men and women across different race groups. The large detrimental impact that smoking already has on public health has the potential to become even greater as the population worldwide ages and dementia prevalence increases.

China study: Compared with light smokers, the adjusted risk of Alzheimer's disease was significantly increased among smokers with a medium level of exposure (RR = 2.56; 95% CI = 1.65-5.52), with an even higher risk of Alzheimer's disease in the heavy smoking group (RR = 3.03; 95% CI = 1.25-4.02). Smoking was associated with the risk of dementia. This study suggests that both smoking status and amount is associated with dementia.

You are ignoring this data.

[L***@wnc.edu]

Post by L***@wnc.edu

Post by Mark Thorson

Post by Lane
Good quality evidence would make me change my mind,
but you have made a general assertion not supported
by the evidence: namely that peroxynitrites cannot
be the cause of Alzheimer's disease because smoking
does not increase the risk for Alzheimer's disease
and that it might actually be protective. The study
did indicate that light smoking slightly decreases
the risk for Alzheimer's disease (although it
slightly increases the risk for vascular dementia).
Many of the compounds in tobacco increase
peroxynitrite levels, but some of the phenolic
compounds which escape oxidation may actually
scavenge peroxynitrites in the brain (hydroquinones,
for instance).

If the protective effect came from other components
of cigarette smoke, the study I linked to earlier
would not have found peroxynitrites in cells exposed
to cigarette smoke.
http://www.researchgate.net/profile/Thomas_Mueller41/publication/14156121_Evidence_for_peroxynitrite_as_an_oxidative_stress-inducing_compound_of_aqueous_cigarette_smoke_fractions/links/00b49536011180da52000000.pdf

Post by Lane
Heavy smoking increases peroxynitrite levels and
the risk for Alzheimer's disease (that there were
only 17 in the study reflects the earlier mortality
rates among heavy smokers). This of course does not
prove that peroxynitrites cause Alzheimer's disease,
but your line of argument does not prove the opposite.

If peroxynitrite were the cause of AD, we'd see much
greater risk in people who chronically dose themselves
with peroxynitrite. Medical ethics wouldn't allow us
to do this directly, but smokers provide a convenient
study population who already do. And they are not at
increased risk for AD. Your study only found increased
risk at the highest dose level, above 2 packs a day.
Not at 2 packs, only above 2 packs. If you're smoking
3 packs a day or more, you've got serious problems just
from that. There has been speculation that hypoxia
may cause AD, and if you're smoking 3 or 4 packs you'll
have a little hypoxia just from the carbon monoxide
exposure reducing the oxygen carrying capacity of your
blood. Not to mention COPD and other impairments to
getting oxygen into the brain.
There are multiple large studies in people, not rodents,
showing either a protective effect or no effect on AD
from smoking, summarized in this meta-analysis.
http://www.researchgate.net/profile/Amy_Borenstein_Graves/publication/230584479_Alcohol_and_tobacco_consumption_as_risk_factors_for_Alzheimer's_disease_a_collaborative_re-analysis_of_case-control_studies/links/0deec53a5a4a677f32000000.pdf
When you ignore data that refutes your pet theory,
you cross the line into crackpottery.

First of all, it is not a matter of no peroxynitrite damage to the brain it is a matter of less peroxynitrite damage to the brain in light smokers versus moderate to heavy smokers. Secondly most heavy smokers don't live long enough to get Alzheimer's disease. If they did, the risk figure would likely be considerably higher.
You have now ignored two studies showing that medium to heavy cigarette use increases the risk for Alzheimer's disease. Certainly it can also increase the risk for vascular dementia and stroke. I will put the conclusions for both studies up for you.
Kaiser study: To our knowledge, this is the first study evaluating the amount of midlife smoking on long-term risk of dementia and dementia subtypes in a large multiethnic cohort. Our study suggests that heavy smoking in middle age increases the risk of both AD and VaD for men and women across different race groups. The large detrimental impact that smoking already has on public health has the potential to become even greater as the population worldwide ages and dementia prevalence increases.
China study: Compared with light smokers, the adjusted risk of Alzheimer's disease was significantly increased among smokers with a medium level of exposure (RR = 2.56; 95% CI = 1.65-5.52), with an even higher risk of Alzheimer's disease in the heavy smoking group (RR = 3.03; 95% CI = 1.25-4.02). Smoking was associated with the risk of dementia. This study suggests that both smoking status and amount is associated with dementia.
You are ignoring this data.

Here is a perhaps an even better explanation for why low levels of smoking decrease the risk for Alzheimer's disease whereas moderate to high levels of smoking increase Alzheimer's disease.

Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells
Zhi-Zhong Guan, , Wen-Feng Yu, Agneta Nordberg

It is plausible that nicotine treatment may play dual effects on oxidative stress and neuroprotection, in which the effects are dependent on the differences in dosage of the drug used and their mechanisms of action. Generally, high dose of nicotine may induce neurotoxicity and stimulate oxidative stress, while reasonably low concentration may act as an antioxidant and play an important role for neuroprotective effect.

http://www.sciencedirect.com/science/article/pii/S0197018603000093

To your credit, you tried to provide a well-reasoned argument why peroxynitrite does not cause Alzheimer's disease. It took you awhile to degenerate to name calling where this is where most people start. You are not the first person to make assumptions about this disease that were not correct. The amyloidist and tauists have been at it for years. But eventually enough evidence will accumulate against these hypotheses that the paradigm will shift to oxidative stress as the cause of Alzheimer's disease.