Skip to main content

A Proteomic Approach for the Involvement of the GAPDH in Alzheimer Disease in the Blood of Moroccan FAD Cases

Journal of Molecular Neuroscience volume 54, pages 774–779 (2014)Cite this article

Abstract

Several articles have highlighted the potential involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in neurodegeneration by showing a non-glycolytic activity of GAPDH specifically in the brains of subjects with Alzheimer’s disease (AD). The novel aim of this study was to elucidate the critical role of GAPDH and its interaction with β-amyloid in the blood of Moroccan patients with familial AD (FAD) carrying presenilin mutations and in sporadic late onset AD (LOAD). Our results show a significant decrease in the activity of GAPDH in blood samples from patients with FAD as compared to sporadic cases and healthy controls. The expression level of GAPDH in brain specimens from mutant tau transgenic mice and patients with FAD was unchanged as compared to healthy controls. In contrast, the expression level of GAPDH in blood samples from mutant tau transgenic mice and patients with FAD was decreased as compared to sporadic cases and healthy controls. Moreover, there is an accumulation of β-amyloid aggregates in the blood samples of patients with FAD and an increase in amyloid fibrils in both the blood and brain samples of these patients. Our study adds new insight to previous ones by showing the involvement of GAPDH in AD, which may influence the pathogenesis of this neurodegenerative disease.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Abramoff MD, Magalhaes PJ, Ram SJ (2004) Image processing with image. J Biophoton Int 11:36–42

    Google Scholar 

  • Butterfield DA, Lauderback CM (2002) Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med 32:1050–1060

    CAS  PubMed  Article  Google Scholar 

  • Butterfield DA, Hardas SS, Lange ML (2010) Oxidatively modified glyceraldehyde-3- phosphate dehydrogenase (GAPDH) and Alzheimer’s Disease: many pathways to neurodegeneration. J Alzheimers Dis 20:369–393

    CAS  PubMed Central  PubMed  Google Scholar 

  • Castellani RJ, Rolston RK, Smith MA (2010) Alzheimer disease. Dis Mon 56:484–546

    PubMed Central  PubMed  Article  Google Scholar 

  • Chen YH, He RQ, Liu Y, Xue ZG (2000) Effect of human neuronal tau on denaturation and reactivation of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase. Biochem J 351:233–240

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Cumming RC, Schubert D (2005) Amyloid beta induces disulfide bonding and aggregation of GAPDH in Alzheimer’s disease. FASEB J 19:2060–2062

    CAS  PubMed  Google Scholar 

  • De Strooper B, Iwatsubo T, Wolfe MS (2012) Presenilins and γ-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006304

    PubMed Central  PubMed  Article  Google Scholar 

  • El Kadmiri N, Zaid N, Zaid Y, Tadevosyan A, Hachem A, Dubé MP, Hamzi K, El Moutawakil B, Slassi I, Nadifi S (2014) Novel presenilin mutations within Moroccan patients with early-onset Alzheimer’s disease. Neuroscience 269:215–222

    PubMed  Article  Google Scholar 

  • Gomez-Ramos A, Smith MA, Perry G, Avila J (2004) Tauphosphorylation and assembly. Acta Neurobiol Exp (Wars) 64:33–39

    Google Scholar 

  • Ling Y, Morgan K, Kalsheker N (2003) Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease. Int J Bioch Cell Biol 35:1505–1535

    CAS  Article  Google Scholar 

  • Mazzola JL, Sirover MA (2001) Reduction of glyceraldehyde-3-phosphate dehydrogenase activity in Alzheimer’s disease and in Huntington’s disease fibroblasts. J Neurochem 76:442–449

    CAS  PubMed  Article  Google Scholar 

  • Nakajima H, Amano W, Fujita A et al (2007) The active site cysteine of the proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase is essential in oxidative stress-induced aggregation and cell death. J Biol Chem 282:26562–26574

    CAS  PubMed  Article  Google Scholar 

  • Naletova I, Schmalhausen E, Kharitonov A et al (2008) Non-native glyceraldehyde-3-phosphate dehydrogenase can be an intrinsic component of amyloid structures. Biochim Biophys Acta 1784:2052–2058

    CAS  PubMed  Article  Google Scholar 

  • Oyama R, Yamamoto H, Titani K (2000) Glutamine synthetase, hemoglobin a-chain, and macrophage migration inhibitory factor binding to amyloid b-protein: their identification in rat brain by a novel affinity chromatography and in Alzheimer’s disease brain by immunoprecipitation. Biochim Biophys Acta 1479:91–102

    CAS  PubMed  Article  Google Scholar 

  • Schulze H, Schuler A, Stuber D et al (1993) Rat brain glyceraldehyde-3-phosphate dehydrogenase interacts with the recombinant cytoplasmic domain of Alzheimer’s B-amyloid precursor protein. J Neurochem 60:1915–1922

    CAS  PubMed  Article  Google Scholar 

  • Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Verdier Y, Huszar E, Penke B et al (2005) Identification of synaptic plasma membrane proteins co-precipitated with fibrillar b-amyloid peptide. J Neurochem 94:617–628

    CAS  PubMed  Article  Google Scholar 

  • Wang Q, Woltjer RL, Cimino PJ et al (2005) Proteomic analysis of neurofibrillary tangles in Alzheimer disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. FASEB J 19:869–871

    CAS  PubMed  Article  Google Scholar 

  • Yang G, Wang L, Zhu M, Xu D (2008) Identification of non-Alzheimer’s disease tauopathies-related proteins by proteomic analysis. Neurol Res 30:613–622

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Ranbanxy Morocco LCC for their partial financial support to Miss Nadia El Kadmiri. We thank Mr. Othman Rouissi at Ranbanxy Morocco LLC and the staff at the CHU IBN ROCHD Neurology Department in Casablanca for their technical assistance. We thank all the staff at CIBERNED—Investigations Center of Neurodegenerative Diseases—the Centro de Biologia Molecular “Severo Ochoa” (Madrid, Spain) for their technical assistance. We also thank the staff at the Medical Genetics Institute at the Universita Catholica in Rome, Italy, for their help in gene sequencing. We thank Dr. B. Elkhalfi at the LPGM for her help.

Conflict of interest

The authors declare that no competing interests exist.

Funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Author information

Affiliations

  1. Laboratory of Medical Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy, University Hassan II, 19 Rue Tarik Ibnou Ziad, B.P. 9154, Casablanca, 20000, Morocco

    Nadia El Kadmiri, Bouchra El Moutawakil, Ilham Slassi & Sellama Nadifi

  2. Laboratory of Physiology and Molecular Genetics, Faculty of Sciences Aïn Chock, University Hassan II, Casablanca, Morocco

    Nadia El Kadmiri & Abdelaziz Soukri

  3. Department of Neurology, CHU IBN ROCHD, Casablanca, Morocco

    Bouchra El Moutawakil & Ilham Slassi

  4. CIBERNED—Investigations Center of Neurodegenerative Diseases—the Centro de Biologia Molecular “Severo Ochoa”, Madrid, Spain

    Raquel Cuardos & Jesus Avila

  5. Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, Montreal, Quebec, Canada

    Ahmed Hachem

Authors
  1. Nadia El Kadmiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel Cuardos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bouchra El Moutawakil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ilham Slassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesus Avila
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sellama Nadifi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ahmed Hachem
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Abdelaziz Soukri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadia El Kadmiri.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

El Kadmiri, N., Cuardos, R., El Moutawakil, B. et al. A Proteomic Approach for the Involvement of the GAPDH in Alzheimer Disease in the Blood of Moroccan FAD Cases. J Mol Neurosci 54, 774–779 (2014). https://doi.org/10.1007/s12031-014-0374-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-014-0374-8

Keywords

  • Moroccan FAD
  • GAPDH