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Evaluation of Sarcopenia Using Biomarkers of the Neuromuscular Junction in Parkinson’s Disease

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Abstract

Patients with Parkinson’s disease (PD) present with an advanced form of age-related muscle loss or sarcopenia. However, the search for a biomarker to accurately predict muscle loss in PD remains elusive. We evaluated the biomarkers of neuromuscular junction (NMJ) stability, including c-terminal agrin fragment-22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of muscle wasting and physical capacity in PD. Male, 63—78 years patients of PD, were investigated for physical capacity, handgrip strength (HGS), and circulating biomarkers at the diagnosis and follow-up during rehabilitation 6 months apart. Patients with PD presented with elevated CAF22 and reduced BDNF and GDNF levels, which were partially restored to normal levels with rehabilitation. All three biomarkers showed significant dynamic associations with HGS and indexes of sarcopenia. Logistic regression revealed that the combination of biomarkers levels into a cumulative risk score enhanced the diagnostic accuracy of sarcopenia. In brief, measurements of plasma BDNF, GDNF, and CAF22 may be helpful in timely diagnosis and/or evaluation of sarcopenia.

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Data Availability

The data is available from the corresponding author on request.

References

  • Bhaskaran S, Pollock N, C Macpherson P, Ahn B, Piekarz KM, Staunton CA, Brown JL, Qaisar R, Vasilaki A, Richardson A, McArdle A, Jackson MJ, Brooks SV, Van Remmen H (2020) Neuron-specific deletion of CuZnSOD leads to an advanced sarcopenic phenotype in older mice. Aging Cell 19(10):e13225

  • Borrione P, Tranchita E, Sansone P, Parisi A (2014) Effects of physical activity in Parkinson’s disease: a new tool for rehabilitation. World J Methodol 4(3):133–143

    Article  Google Scholar 

  • Boyd JG, Gordon T (2003) Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol 183(2):610–619

    Article  CAS  Google Scholar 

  • Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni MP (2019) Writing group for the European working group on sarcopenia in older and E. the extended group for Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48(4):601

    Article  Google Scholar 

  • Daryadel A, Haubitz M, Figueiredo M, Steubl D, Roos M, Mader A, Hettwer S, Wagner CA (2016) The C-terminal fragment of agrin (CAF), a novel marker of renal function, is filtered by the kidney and reabsorbed by the proximal tubule. PLoS One 11(7):e0157905

  • Drey M, Sieber CC, Bauer JM, Uter W, Dahinden P, Fariello RG, Vrijbloed JW (2013) C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction. Exp Gerontol 48(1):76–80

    Article  CAS  Google Scholar 

  • Du Y, Wu HT, Qin XY, Cao C, Liu Y, Cao ZZ, Cheng Y (2018) Postmortem brain, cerebrospinal fluid, and blood neurotrophic factor levels in Alzheimer’s disease: a systematic review and meta-analysis. J Mol Neurosci 65(3):289–300

    Article  CAS  Google Scholar 

  • Erdogan T, Bahat G (2019) Incidence of sarcopenia and dynapenia according to stage in patients with idiopathic Parkinson’s disease. Neurol Sci 40(3):625

    Article  Google Scholar 

  • Hakansson K, Ledreux A, Daffner K, Terjestam Y, Bergman P, Carlsson R, Kivipelto M, Winblad B, Granholm AC, Mohammed AK (2017) BDNF Responses in healthy older persons to 35 minutes of physical exercise, cognitive training, and mindfulness: associations with working memory function. J Alzheimers Dis 55(2):645–657

    Article  CAS  Google Scholar 

  • Hettwer S, Dahinden P, Kucsera S, Farina C, Ahmed S, Fariello R, Drey M, Sieber CC, Vrijbloed JW (2013) Elevated levels of a C-terminal agrin fragment identifies a new subset of sarcopenia patients. Exp Gerontol 48(1):69–75

    Article  CAS  Google Scholar 

  • Karim A, Muhammad T, Qaisar R (2021) Prediction of sarcopenia using multiple biomarkers of neuromuscular junction degeneration in chronic obstructive pulmonary disease. J Pers Med 11(9)

  • Kelly NA, Hammond KG, Bickel CS, Windham ST, Tuggle SC, Bamman MM (2018) Effects of aging and Parkinson's disease on motor unit remodeling: influence of resistance exercise training. J Appl Physiol (1985) 124(4):888–898

  • Krause Neto W, Ciena AP, Anaruma CA, de Souza RR, Gama EF (2015) Effects of exercise on neuromuscular junction components across age: systematic review of animal experimental studies. BMC Res Notes 8:713

    Article  Google Scholar 

  • Kreko-Pierce T, Eaton BA (2018) Rejuvenation of the aged neuromuscular junction by exercise. Cell Stress 2(2):25–33

    Article  Google Scholar 

  • Landi F, Calvani R, Lorenzi M, Martone AM, Tosato M, Drey M, D’Angelo E, Capoluongo E, Russo A, Bernabei R, Onder G, Marzetti E (2016) Serum levels of C-terminal agrin fragment (CAF) are associated with sarcopenia in older multimorbid community-dwellers: Results from the ilSIRENTE study. Exp Gerontol 79:31–36

    Article  CAS  Google Scholar 

  • Landi F, Russo A, Cesari M, Pahor M, Bernabei R, Onder G (2007) HDL-cholesterol and physical performance: results from the ageing and longevity study in the sirente geographic area (ilSIRENTE Study). Age Ageing 36(5):514–520

    Article  Google Scholar 

  • Lima DP, de Almeida SB, Bonfadini JD, de Luna JR, de Alencar MS, Pinheiro-Neto EB, Viana-Júnior AB, Veras SR, Sobreira-Neto MA, Roriz-Filho JD, Braga-Neto P (2020) Clinical correlates of sarcopenia and falls in Parkinson's disease. PLoS One 15(3):e0227238

  • Mandrekar JN (2010) Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol 5(9):1315–1316

    Article  Google Scholar 

  • Martinez-Martin P, Rodriguez-Blazquez C, Mario A, Arakaki T, Arillo VC, Chana P, Fernandez W, Garretto N, Martinez-Castrillo JC, Rodriguez-Violante M, Serrano-Duenas M, Ballesteros D, Rojo-Abuin JM, Chaudhuri KR, Merello M (2015) Parkinson’s disease severity levels and MDS-unified Parkinson’s disease rating scale. Parkinsonism Relat Disord 21(1):50–54

    Article  Google Scholar 

  • Michalski B, Bain JR, Fahnestock M (2008) Long-term changes in neurotrophic factor expression in distal nerve stump following denervation and reinnervation with motor or sensory nerve. J Neurochem 105(4):1244–1252

    Article  CAS  Google Scholar 

  • Phu S, Kirk B, Bani Hassan E, Vogrin S, Zanker J, Bernardo S, Duque G (2020) The diagnostic value of the Short Physical Performance Battery for sarcopenia. BMC Geriatr 20(1):242

    Article  Google Scholar 

  • Piotrowicz Z, Chalimoniuk M, Ploszczyca KK, Czuba M, Langfort J (2019) Acute normobaric hypoxia does not affect the simultaneous exercise-induced increase in circulating BDNF and GDNF in young healthy men: A feasibility study. PLoS One 14(10):e0224207

  • Pratt J, De Vito G, Narici M, Boreham C (2020) Neuromuscular junction aging: a role for biomarkers and exercise. J Gerontol A Biol Sci Med Sci

  • Qaisar R, Karim A, Elmoselhi AB (2020a) Muscle unloading: a comparison between spaceflight and ground-based models. Acta Physiol (Oxf) 228(3):e13431

  • Qaisar R, Karim A, Muhammad T (2020b) Circulating biomarkers of handgrip strength and lung function in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 15:311–321

    Article  CAS  Google Scholar 

  • Qaisar R, Karim A, Muhammad T (2020c) Plasma CAF22 levels as a useful predictor of muscle health in patients with chronic obstructive pulmonary disease. Biology (Basel) 9(7)

  • Qaisar R, Karim A, Muhammad T, Shah I (2020d) Circulating biomarkers of accelerated sarcopenia in respiratory diseases. Biology (Basel) 9(10)

  • Qaisar R, Karim A, Muhammad T, Shah I, Khan J (2021) Prediction of sarcopenia using a battery of circulating biomarkers. Sci Rep 11(1):8632

    Article  CAS  Google Scholar 

  • Sakuma K, Yamaguchi A (2011) The recent understanding of the neurotrophin's role in skeletal muscle adaptation. J Biomed Biotechnol 2011:201696

  • Sataranatarajan K, Qaisar R, Davis C, Sakellariou GK, Vasilaki A, Zhang Y, Liu Y, Bhaskaran S, McArdle A, Jackson M, Brooks SV, Richardson A, Van Remmen H (2015) Neuron specific reduction in CuZnSOD is not sufficient to initiate a full sarcopenia phenotype. Redox Biol 5:140–148

    Article  CAS  Google Scholar 

  • Scherbakov N, Knops M, Ebner N, Valentova M, Sandek A, Grittner U, Dahinden P, Hettwer S, Schefold JC, von Haehling S, Anker SD, Joebges M, Doehner W (2016) Evaluation of C-terminal agrin fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation. J Cachexia Sarcopenia Muscle 7(1):60–67

    Article  Google Scholar 

  • Sobestiansky S, Michaelsson K, Cederholm T (2019) Sarcopenia prevalence and associations with mortality and hospitalisation by various sarcopenia definitions in 85–89 year old community-dwelling men: a report from the ULSAM study. BMC Geriatr 19(1):318

    Article  Google Scholar 

  • World Medical A (2013) World medical association declaration of helsinki: ethical principles for medical research involving human subjects. JAMA 310(20):2191–2194

    Article  Google Scholar 

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Funding

This work was supported by Target (1901090168) and competitive grants (1901090157 and 2001090177) from the University of Sharjah to Rizwan Qaisar.

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Authors and Affiliations

  1. Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates

    Asima Karim & Rizwan Qaisar

  2. University of Health Sciences, Lahore, Pakistan

    Asima Karim

  3. Department of Neurology and Stroke Medicine, Rehman Medical Institute, Peshawar, 25124, Pakistan

    M. Shahid Iqbal

  4. Department of Biochemistry, Gomal Medical College, Gomal University, Dera Ismail Khan, 30130, Pakistan

    Tahir Muhammad

Authors
  1. Asima Karim
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  2. M. Shahid Iqbal
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  3. Tahir Muhammad
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  4. Rizwan Qaisar
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Contributions

Conceptualization; R.Q & M.I Data curation; R.Q, A.K, M.I & T.M Formal analysis; R.Q & A.K Funding acquisition; R.Q Investigation; R.Q, A.K & M.I Methodology; A.K & M.I Project administration; A.K & M.I Resources; R.Q, A.K, T.M & M.I Supervision; R.Q, A.K & M.I Validation; R.Q & A.K Writing—original draft; R.Q & T.M Writing—review & editing, R.Q & T.M.

Corresponding author

Correspondence to Rizwan Qaisar.

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Ethics Approval

The ethics approvals were obtained from the regional ethics committees at the University of Health Sciences, Lahore, and the Department of Neurology and Stroke Medicine, Rehman Medical Institute, Peshawar Pakistan.

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The consent was obtained from all participants before recruitment into the study.

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The consent for publication was obtained from all the study participants, as well as the authors.

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The authors declare no competing interests.

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Karim, A., Iqbal, M.S., Muhammad, T. et al. Evaluation of Sarcopenia Using Biomarkers of the Neuromuscular Junction in Parkinson’s Disease. J Mol Neurosci 72, 820–829 (2022). https://doi.org/10.1007/s12031-022-01970-7

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  • DOI: https://doi.org/10.1007/s12031-022-01970-7

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