I remember a podcast with one of the guys at the Buck Institute and apparently its a pretty easy, quick and inexpensive test (In the Timeline trial, you just dripped a few drops of blood on a piece of paper and sent it to them). Someone needs to create a commercial version of this test - perhaps if a bunch of us emailed a few test labs like Merek, and Life Extension foundation, they would offer it.
lower TC levels were associated with lower composite scores of frontal/executive function and a higher future risk of PDD conversion in the under-/normal weight group, whereas higher TC levels were associated with poor performance on frontal/executive items and more frequent PDD conversion in the obese group. These findings indicate that the association between TC levels and cognition is moderated by BMI in patients with PD, suggesting that a cholesterol-lowering strategy could be applied differentially according to BMI.
Clinical studies have demonstrated that individuals with high levels of circulating TC are less likely to develop PD and have better long-term outcomes.
A recent investigation discovered that elevated cholesterol levels have a dual role in PD: they protect against lysosomal membrane permeabilization while also promoting α-synuclein accumulation
When examining the association between cholesterol levels and Alzheimer’s disease or vascular dementia, previous studies have shown inconsistent results, and this association seems to vary with age at measurement (mid-life [< 65 years] or later life [≥ 65 years]) and follow-up duration
Causal relationships could not be assessed in this study, and reverse causation should also be considered. For example, because TC levels are biomarkers of malnutrition, patients with PD who have low TC levels in the under-/normal weight group may be malnourished, which subsequently leads to poor cognitive outcome. In addition, a recent study showed that familiar patients with PD, particularly those with a glucocerebrosidase (GBA) mutation, have lower cholesterol levels than healthy controls and patients with sporadic PD. Considering the fact that GBA is associated with poor cognitive performance and the risk of PDD, poor cognitive outcomes in patients with PD and low TC levels in the under-/normal weight group may be attributed to underlying genetic risk factors.
We found that both rapamycin and CTEP induced a significant reduction of α-syn fibrils in SH-SY5Y cells and this effect was associated with a reduction in mTOR signaling and enhancement in autophagic pathway factors. These data support the possibility that CTEP (or rapamycin) might be a useful pharmacological approach to target abnormal α-syn accumulation by promoting intracellular degradation or enhanced clearance.
There appears to be some linkage between age-related essential tremors and Parkinson’s disease.
FWIW:
Before I started rapamycin, I am 82 years old, I was experiencing age-related essential tremors. After a few months of rapamycin, they completely disappeared. This was something I was not expecting and did not notice it until it occurred to me that my hands were not shaking when eating.
This study was of course on mice, but it certainly gives some hope.
“Rapamycin can effectively alleviate symptoms of PD”
Thanks for this - very interesting. What dose of rapamycin are you taking? As far as PD goes, I am interested for a patient of mine with very early symptoms. I’ve had a mild essential tremor for years and have been on the rapa for less than 3 months ago I’m looking forward to seeing if any of those things change.
I was following a suggested protocol at the time based on Dr. Mikhail V. Blagosklonny’s work and Twitter feeds.
So like most here, I am self-experimenting. I started off with 5mg/week with EVOO then tried 20mg with GFJ and EVOO once every two weeks.
Blagosklonny’s recommendation at the time was pulse dosing at the maximum amount that did not produce unwanted side effects. The 2-week pulse regimen is based on allowing 5 half-lives to occur between doses. The current popular 1-week regimen is apparently based on mTOR modulation. The 20mg with GFJ and EVOO may have been equivalent to ~40 to 80 mg of rapamycin. Some will think this is a foolishly high dose, but it has been pointed out that even massive overdoses produced no lasting adverse effects.
The 20mg with GFJ produced mild diarrhea on the second and third days after taking the dose.
I now am titrating back up to the max I can take with GFJ. Right now I am taking 5mg/week with GFJ and EVOO. This dose produces no apparent side effects. I get blood work regularly and try to keep my lipids in the “normal” range.
I am 82 and a self-experimenter and do not recommend to anyone to follow anything I do.
Most studies for longevity indicate higher doses for longer lifespans.
These charts have been posted before, but I will save you the trouble of looking for them.
There doesn’t seem to be much in the way of online evidence, does there? But I have PD and I’m trying it–8mg/week since December. Had PD for 8 years…can’t say I see much difference yet and wonder if I should dial it up. But I also fast and eat keto, so maybe that’s confounding?
I think the effects are likely to be slower than that. In terms of dialling it up, have you had any side effects at 8mg? It probably depends on your age and weight as well. Are you taking meds for the PD?
Ha, yes, I guess I know that. Really, the best I hope for is a slowing or (dare I say) stopping of progression, and of course, that’s nearly impossible to measure.
No side effects yet (keep waiting for pimples!) and I wonder about dialing it up but I’m a little scared. I’m 66 (as of yesterday, actually! :o) and pretty tall + skinny. 140lbs.
My symptoms are still one-sided. I don’t take any dopamine. I take rasagiline because when I was diagnosed there was a study that suggested a hint of neuroprotection and my Dr. was all over it. Not sure it does much.
I take a stack of supplements–the usual, probably, for this crowd. What I believe (with no hard evidence) has helped the most is exercise and DIET–as I said I eat keto, and fast. And oh yes, I have a GBA mutation…if that means anything to you.
I have Parkinson’s since December 2020. I do not take any medication! Since three weeks I take 5 mg rapamycin a week. I have published a video about my alternative healing methods:
Zone 2 exercise (as defined by Iñigo San Millán ) is important for mitochondria (improvement in density and amount of mitochondria) but it is unclear to me how it affects systemic mitochondria amount rather than local (exercised muscles, possibly nearby organs). Like the brain.
I understand it is possible for mitochondria to be transferred although I think rare hence autophagy/mitophagy has to be stimulated in the specific cells. There are lots of ways of doing this. Rapamycin is good in systemically doing this. Other stimulations of HIF 1 alpha such as a reduction in partial pressure of Oxygen mainly done through HBOT.
I am currently having a good go with Red Light and Near Infra Red, but that will only go part way into the skull possibly an inch or so.
I wonder how good PEMF is. I have paid for a Hugo Intense device, but not got it yet.
One thing to be careful about is glucose handling as high levels of glucose inhibit autophagy.
Please continue to update us on this. I have a friend recently diagnosed with this. I suspect that rapamycin has potential to greatly slow or stop parkinsons.
