My PCP finally agreed to run Cystatin and NFL blood biomarker tests for me.

[House2]

The FDA defines a biomarker as a specific  characteristic that is measured (such as a chemical in the blood) which can be used to indicate how "normally" biological processes are functioning, the severity of pathogenic processes, and most importantly how the body is responding  (improving or worsening) to a disease, including how a patient is responding to a given treatment. 

 A biomarker is not an assessment of how an individual feels, but rather an assessment of the course and direction of the disease process, independent of the patient’s signs and symptoms.

Thus biomarkers serve as a window to objectively observe the underlying disease process in a patient.  Most importantly they provide evidence if a specific treatment is merely improving symptoms or physiologically changing and therapeutically modifying the actual  course of the disease.

Cystatin C,  S100B Protein and Neurofilament Light-chain are blood borne chemicals, easily accessible through routine blood testing that are promising Parkinson’s Disease biomarkers.

 A number of published studies suggest these biomarkers can be useful in predicting disease progression, the degree of neuroinflammation, and the risk of cognitive decline in people diagnosed with PD.

 Sadly, there are no currently available disease modifying medications in use for the treatment of PD. Without any disease modifying treatments to offer their PD patients, it is not surprising that Movement Disorder Specialists have shown little interest in PD biomarkers.

 We as patients have an opportunity to by-pass the MDS and directly demonstrate if our alternative treatments (B1, Cinnamon, Broccoli, etc.) can modify the underlying PD process. 

 It may be as simple as having a blood test, starting an alternative treatment, then having a follow-up blood test after several months.       

I'll report my lab results when I get them. 

 

Cystatin widely available: (Test Code 121251: Cystatin C | Labcorp, n.d.)

 NFL available at select locations: (Test Code 140455: Neurofilament Light Chain, Serum | Labcorp)

 S100B very limited availability: (Test Code 6905139: S-100B PROTEIN, SERUM | LABCORP OKLAHOMA, INC. | Test Directory, n.d.)

UPDATE: I found a lab that does the S100-b protein blood test (need to figure out the logistics)

2001766 / S-100B Protein, Serum

Out of pocket price is $41.62 subject to change.

aruplab.com

>>>>>>>>>>>>

Aamodt, W. W., Waligorska, T., Shen, J. (2021). Neurofilament Light Chain as a Biomarker for Cognitive Decline in Parkinson Disease. Movement Disorders: Official Journal of the Movement Disorder Society, 36(12), 2945–2950. doi.org/10.1002/mds.28779

Angelopoulou, E., Paudel, Y. N., & Piperi, C. (2021). Emerging role of S100B protein implication in Parkinson’s disease pathogenesis. Cellular and Molecular Life Sciences: CMLS, 78(4), 1445–1453. doi.org/10.1007/s00018-020-...

Dong, X., Zheng, D., & Nao, J. (2019). Measurement of serum cystatin C: A valuable tool for evaluating dyskinesia in Parkinson’s disease. Neuroscience Letters, 705, 172–176. doi.org/10.1016/j.neulet.20...

Imarisio, A., Pilotto, A., Garrafa, E (2021). Plasma Cystatin C Correlates with Plasma NfL Levels and Predicts Disease Progression in Parkinson’s Disease. Neuro-Degenerative Diseases, 21(5–6), 109–116. doi.org/10.1159/000523982

Michetti, F., D’Ambrosi, N., Toesca, A (2019). The S100B story: From biomarker to active factor in neural injury. Journal of Neurochemistry, 148(2), 168–187. doi.org/10.1111/jnc.14574

Mollenhauer, B., Dakna, M. (2020). Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson’s Disease Progression. Movement Disorders: Official Journal of the Movement Disorder Society, 35(11), 1999–2008. doi.org/10.1002/mds.28206

Park, D. G., Kim, J (2021). Plasma neurofilament light chain level and orthostatic hypotension in early Parkinson’s disease. Journal of Neural Transmission (Vienna, Austria: 1996), 128(12), 1853–1861. doi.org/10.1007/s00702-021-...

Research, C. for D. E. and. (2021). About Biomarkers and Qualification. FDA. fda.gov/drugs/biomarker-qua...

Schaf, D. V., Tort, A. B. (2005). S100B and NSE serum levels in patients with Parkinson’s disease. Parkinsonism & Related Disorders, 11(1), 39–43. doi.org/10.1016/j.parkreldi...

Yang, C.-G., Cai, S.-M., Liu, C.-Y., & Chen, C. (2021). On the correlation between serum Cystatin C and Parkinson’s disease in the Chinese population: A promising biomarker? Journal of Integrative Neuroscience, 20(2), 349–357. doi.org/10.31083/j.jin2002034

Yardan, T., Erenler, A. K., Baydin, A., Aydin, K., & Cokluk, C. (2011). Usefulness of S100B protein in neurological disorders. JPMA. The Journal of the Pakistan Medical Association, 61(3), 276–281.

Ygland Rödström, E., (2022). Serum Neurofilament Light Chain as a Marker of Progression in Parkinson’s Disease: Long-Term Observation and Implications of Clinical Subtypes. Journal of Parkinson’s Disease, 12(2), 571–584. doi.org/10.3233/JPD-21286

[Smittybear7]

How many does the blood test cost.? If the dr won't order it where can you get the test done and who do you get to read them? Good luck to you.

[Little_apple]

Very interesting and actionable. Are you trying to gauge your level of autophagy?

CYS C = Cystatin C

“Our study provides evidence that may aid in the development of an alternative approach for the treatment of PD through modulation of CYS C-mediated neuronal-vascular pathways.”

“Taken together, these findings strongly suggest that CYS C could be a novel secreted protein that induces cellular autophagy and induces angiogenesis in the cerebral microenvironment.”

The current study shows that CYS C is a potential mediator functioning to induce angiogenesis and enhance cellular autophagy in the NVUs of PD models.

ncbi.nlm.nih.gov/pmc/articl...

Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer's and Parkinson's diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C.

Autophagy has been shown to be suppressed in the striatum of a transgenic mouse model of Parkinson’s disease. Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C. It has been suggested that cystatin C plays the primary role in amyloidogenesis and shows promise as a therapeutic agent for neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases).

Controlled expression of a cystatin C peptide has been proposed as a new approach to therapy for Alzheimer’s disease. In Parkinson’s disease, serum cystatin C levels can 

vavilov.elpub.ru/jour/artic...

Cystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases.

nature.com/articles/cddis20...

Neuroprotective effects of CysC were prevented by inhibiting autophagy with beclin 1 siRNA or 3-methyladenine. Our findings show that CysC plays a protective role under conditions of neuronal challenge by inducing autophagy via mTOR inhibition and are consistent with CysC being neuroprotective in neurodegenerative diseases. Thus, modulation of CysC expression has therapeutic implications for stroke, Alzheimer's disease, and other neurodegenerative disorders.

ncbi.nlm.nih.gov/pmc/articl...

***My interpretation of this data is that Cystatin C plays an important role in autophagy and therefore increased levels of Cystatin C could be indicative of a response to abnormal neuronal functioning. I am interested in learning more about Cystatin C as a peptide and how it inhibits MTOR. ***

[House2 in reply to Little_apple]

FYI'

us.supersmart.com/article.p...

[Little_apple in reply to House2]

Thank you. Do you use this? I’m not aware of white willow.

Berberine also decreases MTOR

[House2 in reply to Little_apple]

white willow is an aspirin like herb. No I am limited in what I can take, I'm on blood thinners.

[gomelgo in reply to House2]

What is mTOR please?

[Little_apple]

Neuro filament Light / NFL

Longitudinal studies in multiple sclerosis, traumatic brain injury, and stroke show accumulation of NfL over days followed by elevated levels over months. Therefore, it may be hard to determine with a single measurement when the peak of NfL is reached and when the levels are normalized. Nonetheless, measurement of blood NfL provides a new blood biomarker for neurologic diseases overcoming the invasiveness of CSF sampling that restricted NfL clinical application. In this review, we examine the use of blood NfL as a biologic test for neurologic disease.

ncbi.nlm.nih.gov/pmc/articl...

[gomelgo in reply to Little_apple]

I have been carrying around a script for this test for a few months now. The doc who prescribed it, did so on my request, and said she would not know how to read the results, and besides she was in her last week of practice. So if anyone knows what type of doctor I should look for to be able to understand the results, I would be ever so grateful.

[House2 in reply to gomelgo]

There should be a reference range (normal) provided with your test results.

[Little_apple in reply to gomelgo]

ifm.org/?hsa_kw=institute%2...

[House2 in reply to Little_apple]

R U a. Practitioner?

[Little_apple in reply to House2]

No unfortunately

[104L]

Has anybody been tested for CRP? Results? My wife is PWP for 20 years and 75. Her doctor ordered test two years ago was 7mg/L and is now 33 mg/L. This test was regular CRP not the high sensitivity CRP test which has a different metric.

[House2 in reply to 104L]

I do/have done CRP high sensitivity, is your wife pre-diabetic?

[104L in reply to House2]

Wife is not prediabetic but she does have a pressure ulcer on her heel that has not resolved. PCP wants to wait several weeks and then test CRP again. I realize that a 33 mg/L CRP is well above normal for a healthy person but I don’t know how unusual it is for a 75 year old person that has had Parkinsons for 20 years. Thanks.

[enjoy2013]

House2,

Very well done. I am a physician and pwPD, and I agree with what you did, and I am awaiting these tests to be made available here to do the same for myself.

I would just say that drawing information requires previous data, ie your l-nfl was at some level for 2 years and since you started high dose thiamine, it dropped by 50%, and stayed low at 3 and 6 months.

But I guess you know that .

May I ask, are you based in the US?

[House2 in reply to enjoy2013]

Yes, USA

[enjoy2013]

OK

[House2 in reply to enjoy2013]

cystatin c should be available in the UK, I think.

[6daniparky]

Molto interessante, grazie.

[Hikoi]

, it is not surprising that Movement Disorder Specialists have shown little interest in PD biomarkers.

What have MDS’ got to do with interest in biomarkers? It is researches who are focusing on this isnt it? ( i believe MDS are indeed interested in biomarkers and feel hampered by the lack of any.)

[House2 in reply to Hikoi]

My expectation is/was that a "specialist" should be well versed in emerging research, including blood borne biomarkers like aSYN, CYS-C, NFL and S100b.