What if everyone has Parkinson's?

The question

Sometimes if you look at things from a different perspective it gets you thinking in useful ways. Sometimes it does not. With those two conflicting thoughts in mind, let me ask the question:

What if everyone has Parkinson's?

I don't mean: what if everyone suddenly developed PD symptoms? What I do mean is: what if everyone has Parkinson's to a greater or lesser extent? In such a world things are not black and white, e.g. he has PD/ he doesn't have PD; but, rather, things are all shades of grey, e.g. she has 7% PD/ she has 94% PD.

Does such a model match the real world? In my view surprisingly well.

Inductive Justification

Looking back from diagnosis, if you were diagnosed today, does that mean that you didn't have Parkinson's yesterday? Of course not. Many PwP report years of symptoms before diagnosis. And, suppose, that there's a day when you noticed your first symptom (although you didn't recognize it as such at the time) does that mean that you didn't have any earlier unrecognised symptoms or signs. Again, of course not. So, it's possible that a PwP never had 0% Parkinsons.

Looking foward from diagnosis, the disease is progressive, symptoms get worse. The Parkinson's that a newly diagnosed PwP experiences is much less debilitating than the Parkinson's of a long time sufferer. In this model the new PwP would be said to have less than 100% Parkinson's.

Epidemiological Justification

Now the argument so far relates to people who are or who become PwP. It could be that PwP are a special class of person, so that this argument only applies to them. But I note that the epidemiological data shows an increasing prevalence of PD as people get older. Extrapolating, it seems to me to be not unreasonable to suggest that everyone who survived to 150, say, would have Parkinson's. This suggests that everyone can become a PwP, and that the working backwards argument could apply to everyone.

Biological Justification

There could be variations across the whole population in the number of dopaminergic neurons in the substantia nigra and the rate at which they are dying. Circumstantial evidence in support of this is found in a paper by Baker et al. [1] who compared two strains of mice and found differences in the number of neurons across the brain ranging from 26% to 38% (see their Table H).

Using post-mortem, normal human brains (average age 84), Damier et al. [2] counted the number of dopamine-containing neurons per half brain and, across 5 brains, got a mean of 199251 with a standard error of the mean of 18446. With such a small sample size it is dangerous to extrapolate these figures, but they imply a standard deviation of about 40000 or about 20% of the mean. This, in turn, implies that about 2.5% of the population have less than 60% of the average of this type of neuron.

There appears to be a decline of dopamine D1 receptors in the brain with normal ageing. For instance, Wang et al. report [3]:
"We found an age-dependent decrease of D1 receptor binding in the caudate (6.9% per decade) and putamen (7.4% per decade). There was also a significant inverse correlation between [11C]SCH 23390 binding in the occipital cortex and age (8.6% decline per decade)."

Consequences

Parkinson's would not be seen as an old person's disease. This would suggest that life style and environmental changes should be targeted at all ages. (For instance, compare the target audiences for health messages sent for obesity and Parkinson's.)

The impact of the disease are probably far wider than normally assumed. (The pre-diagnosis stage has a cost and, possibly, for every diagnosed person there are dozens of never to be diagnosed people whose quality of life is nevertheless reduced.)

Trials on "normal" people could be used to supplement data from PwP.

References

[1] "VARIATIONS IN NUMBER OF DOPAMINE NEURONS AND TYROSINE HYDROXYLASE ACTIVITY IN HYPOTHALAMUS OF TWO MOUSE STRAINS"
HARRIET BAKER,2 TONG H. JOH, DAVID A. RUGGIERO, AND DONALD J. REIS
JOurnal of Neuroscience, April 1983
http://www.jneurosci.org/content/3/4/832.full.pdf

[2] "The substantia nigra of the human brain"
Damier P, et al.
Brain (1999), 122, 1421-1436
http://web.mit.edu/bcs/graybiel-lab/...in_Damier2.pdf

[3] "Age-dependent decline of dopamine D1 receptors in human brain: A PET study"
Yue Wang1, Grace L.Y. Chan1, James E. Holden2, Teresa Dobko1, Edwin Mak1, Michael Schulzer1, Joseph M. Huser1, Barry J. Snow1, Thomas J. Ruth1, Donald B. Calne1, A. Jon Stoessl
Synapse, vol 30 issue 1
http://onlinelibrary.wiley.com/doi/1...44AADC4.d01t04

John

Hi John,
Yes, I think you have smething there. It would fit in well with the BBB theory. We are not all born with the same BBB permebility, or the same length of nose!! Then as we age, our BBB permeability increases. Some will reach the threshold level sooner than others, and start to show PD symptoms. Supporting evidence for the BBB theory was published recently by London University.
Ron

Our very first neuro told us that if we lived long enough, we would all get PD. I dont' know how long that would be, though, as we had several near-100 years old in our families and no one had PD.

But I think your point is analogous to cancer. Science tells us that all of us have cancer cells everywhere, it's just when they get aggressive enough to form a tumor that we know about it. Medical students studying cadavers routinely find cancer growths in "healthy" people. And Ron's points are also convicing: we are born with different BBB permeabilities, stress responses, etc.

It would be interesting to know how long people lived in India thousands of years ago, when PD was first crudely described-it was around that long ago albeit on a much smaller scale. Makes you wonder.

There's a theory making the rounds (still a theory, although there have been papers written on it) that all neurodegenerative diseases are really variations of "Type III diabetes." This fits in neatly with the mitochondrial explanation that has been mentioned on other threads, as the consequences of inflammation produced by insulin resistance and too much circulating glucose is ultimately cellular damage due to reactive oxygen species (ROS).

My WAG is that whether you get PD, Alzheimer's, multiple sclerosis, ALS, or Huntington's will depend on your personal genetic makeup. If you get PD, then how early your nigral cells start to die also depends on your individual sensitivities - just as not all people who drink eight Cokes a day go on to develop Type II diabetes, and not all people who smoke get lung cancer.

A brief piece in New Scientist says:

So, at death 15% of the "normal" brains show signs of neurodegenerative disease.

Reference

[1] New Scientist "Life savings: Inside London's brain bank"
http://www.newscientist.com/article/...rain-bank.html

John