Present studies are underway as we speak to determine if the protein alpha synuclein is a factor in Parkinson's.

If it is true that alpha synuclein may cause Parkinsons, could a blood cleansing machine which filters blood reduce alpha synuclein? The study below shows that red blood cells contain 99% of alpha synuclein (AS).

Imagine if a machine quite similar to a dialysis machine could be used perhaps 3 to 4 times a year to clear the AS! This could be used until the source of excess AS could be found. Would you be willing to have your blood cleaned to be symptom free? I sure would?

The research goes on!

Happy Thanksgiving Everyone!

Red blood cells are the major source of alpha-synuclein in blood. - PubMed - NCBI

I think that this is a very interesting paper.

One thing that I wonder about is whether or not alpha-synuclein from red blood cells or CSF or plasma can be taken up by neurons in the substantia nigra part of the basal ganglia complex.

In theory this would be easy to test in animal models, seeing if uptake can happen.

If it does happen that would represent a new therapeutic approach for PD (ie, working out how to block alpha-synuclein uptake by those neurons).

We need alpha-synuclein for a healthy brain. Misfolded alpha-synuclein, a prion, causes the issues. I really suspect we will see a vaccine in five to ten years to address this.

Prions are proteins that adopt alternative conformations that become self-propagating;

Just fascinating, I'll admit I have to read through this a few times to get a basic understanding. Lots to learn:

Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. SNCA synuclein alpha [Homo sapiens (human)] - Gene - NCBI

A good idea!

My initial reaction was that the BBB would make this impossible, but I was wrong.

Working with mice, Sui et al. report [1]:

"plasma levels of α-Syn are hundreds of times higher than its CSF levels".

"α-Syn is transported across the BBB bidirectionally, in both the brain-to-blood and blood-to-brain directions."

"Inflammation as induced by Lipopolysaccharide increases alpha-synuclein entry into brain, probably because of BBB disruption".

For this approach to be reasonable, we still need to show that PwP can function on lower levels of alpha-synuclein, that lower levels of alpha-synuclein lead to reduced aggregation and, indeed, that these aggregations play a causal role in the pathogenesis of PD. Finally, can such filters be built?

Reference

[1] "Alpha Synuclein is Transported Into and Out of the Brain by the Blood-brain Barrier"
Yu-Ting Sui,1 Kristin M. Bullock,2 Michelle A. Erickson,2 Jing Zhang,1 and W. A. Banks
Peptides, Dec 2014
Alpha Synuclein is Transported Into and Out of the Brain by the Blood-brain Barrier

John

We may be able to get an indication of whether filtering alpha-synuclein out of the body can reduce PD without testing it directly. There are three classes of people who have had related experiences:

- healthy people who have has transfusions of blood from donors with Parkinson's. If there is something in the blood of PwP that can "infect" someone, these people would be expected to have an increased chance of getting PD. It is reported [1] that there is no evidence of this:

"A retrospective study of nearly 1.5 million patients over the course of 44 years showed no evidence to support the claim that neurodegenerative disorders can be transmitted between individuals through blood transfusions."

- people with Parkinson's who had blood transfusions of healthy blood. These PwPs would be expected to have slower progression. Olsen asked the question "Fresh Blood Transfusion a possible treatment?" in a 2014 thread [2]:

"old mice get better at learning and remembering when they have young blood circulating in their brains."

- people on dialysis already have their blood filtered now. Does this capture alpha-synuclein? If it does, the hypothesis would be that dialysis would lead to a decreased chance of PD and a slower progression

Of course, these interventions involve more than alpha-synuclein, and by the very ad hoc nature of these events they are not best able to detect changes. That said, just one case study linking these effects would be interesting.

References:

[1] No evidence to show Alzheimer’s or Parkinson’s transmission via blood transfusion | Clinical Neurology News

[2] Fresh Blood Transfusion a possible treatment?

John

Excellent research John,

The Frontline article may indicate that alpha synuclein isn't a factor in PD. Alternatively, maybe it takes decades of buildup of alpha synuclein to cause PD which one would not get from occasional blood transfusions. Maybe AS is still the culprit but one would have to be subjected to excess AS over several decades before the damage takes its toll! Interesting research! I am hopeful that the 5 AS studies underway will reveal more in the coming year!

You have to remember, as TexasTom wrote, that it is misfolded a-syn that is the culprit, not properly folded a-syn which is an essential protein that enables neurotransmitters in the body. Another issue is, which TexasTom didn't get exactly right, is that misfolded a-syn is not an actual prion (e.g. Creutzfeldt-Jakob disease), but rather prion-like. There is a difference as a prion is self-derived, self-sustaining, and infectious. Alpha synuclein, being prion-like, is believed like other neurological misfolded proteins (e.g. amyloid, tau, etc.) to be what is now referred to as a transcellular prionoid. Prionoids are proteins that demonstrate prion-like propagation between cells within a disease context (e;g. Alzheimer's or PD) but have limited evidence for organism infection or transmission.

PubMed Central Image Viewer.

With regard to blood filtering, it would the misfolded prionoid a-syn that you would want to remove, not necessarily all a-syn. This is what the vaccines we have been following target. I'm not aware of any research showing that people on dialysis have a lower instance of Parkinson's. Alternatively, I have seen research that shows that people with end-stage-renal-disease (ESRD) have a significantly higher chance of developing PD. These people would all be on dialysis.

Great analysis Tupelo. The Parkinson's blood filter would require the dialysis filtration to be changed to filter out AS not blood/kidney toxins. Reducing misfolded AS seems to be the goal, although I'm not sure present technology can filter out only misfolded AS using an assay. I think the idea with Prothena is to reduce overall AS in the hopes that will result in lower misfolded AS and thus improve symptoms. Everyone has AS so I'm not sure what levels of AS are considered to be normal. Perhaps these studies on AS will determine that.