Qualitative Proteomics Analysis of Proteins and Biomarkers of Alzheimer’ Disease

Maheen Rasheed, Kashif Kareem, Aliha Liaquat, Aneela Ashraf, Sania Maryam


Alzheimer’sdementia (AD) is the plague of today's world: a costly harming illness that ransacks the elder of their capacity to work and affect their recollections. Many years of research have brought about a profound comprehension of the pathological processes and a range of targets of therapy. Proteomics has contributed enormously to these advances and will keep on having a growing role in determining the nature of obsessive injuries. Moreover, proteomics (both gel-based and gel-free, mass spectrometry-based), is probably going to assume an expanding job in distinguishing biomarkers that may aid early determination and in observing movement and above all response therapy. Alzheimer's dementia is a neurodegenerative disease characterized by limited motor functions and loss of memory. Clinically it is diagnosed by accumulation of plaques in neurons and formation of NFTs by the aggregation of tau proteins. These pathological changes in the brain can be observed in preclinical stages of AD known as ASYM AD and mild cognitive dementia.


Biomarkers; Dementia; Enormously; Neurodegenerative; Pathologica

Full Text:



Arnold, S. E., Hyman, B. T., Flory, J., Damasio, A. R., and Van Hoesen, G. W. (1991). The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebral Cortex, 1(1), 103-116.

Asif, M. (2020). Coronavirus (COVID-19) Symptoms, Treatment and Recent Medical Challenges to the World: A Review. Journal of Preventive Medicine, 5(4), 20.

Braak, H., Braak, E., Grundke-Iqbal, I., and Iqbal, K. (1986). Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neuroscience Letters, 65(3), 351-355.

Caselli, R. J., and Reiman, E. M. (2013). Characterizing the preclinical stages of Alzheimer's disease and the prospect of presymptomatic intervention. Journal of Alzheimer's Disease, 33(s1), S405-S416.

Chan, H. L., Gharbi, S., Gaffney, P. R., Cramer, R., Waterfield, M. D., and Timms, J. F. (2005). Proteomic analysis of redox‐and ErbB2‐dependent changes in mammary luminal epithelial cells using cysteine‐and lysine‐labelling two‐dimensional difference gel electrophoresis. Proteomics, 5(11), 2908-2926.

Citron, M. (2010). Alzheimer's disease: strategies for disease modification. Nature reviews Drug discovery, 9(5), 387-398.

Deng, Y., Li, B., Liu, Y., Iqbal, K., Grundke-Iqbal, I., and Gong, C.-X. (2009). Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: Implication for Alzheimer’s disease. The American journal of pathology, 175(5), 2089-2098.

Desikan, R. S., Cabral, H. J., Settecase, F., Hess, C. P., Dillon, W. P., Glastonbury, C. M., Weiner. M. W., Schmansky. N. J., Salat. D. H., and Fischl, B. (2010). Automated MRI measures predict progression to Alzheimer's disease. Neurobiology of aging, 31(8), 1364-1374.

Dodge, H. H., Zhu, J., Woltjer, R., Nelson, P. T., Bennett, D. A., Cairns, N. J., Fardo. D. W., Kaye. J. A., Lyons. D., Mattek. N., Schneider. J. A., Silbert. L. C., Xiong. C., Yu. L., Schmitt. F. A., Kryscio. R. J., and Abner. E. L. (2017). Risk of incident clinical diagnosis of Alzheimer's disease–type dementia attributable to pathology-confirmed vascular disease. Alzheimer's and Dementia, 13(6), 613-623.

Doecke, J. D., Laws, S. M., Faux, N. G., Wilson, W., Burnham, S. C., Lam, C.-P., and Brown, B. (2012). Blood-based protein biomarkers for diagnosis of Alzheimer disease. Archives of neurology, 69(10), 1318-1325.

Driscoll, I., and Troncoso, J. (2011). Asymptomatic Alzheimer's disease: A prodrome or a state of resilience? Current Alzheimer Research, 8(4), 330-335.

Du, C., Ramaley, C., McLean, H., Leonard, S. C., and Miller, J. (2005). High-performance liquid chromatography coupled with tandem mass spectrometry for the detection of amyloid beta peptide related with Alzheimer’s disease. Journal of Biomolecular Techniques: JBT, 16(4), 356.

Fagan, A. M., and Perrin, R. J. (2012). Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomarkers in Medicine, 6(4), 455-476.

Gibson, G. E., Park, L. C., Zhang, H., Sorbi, S., and Calingasan, N. Y. (1999). Oxidative stress and a key metabolic enzyme in Alzheimer brains, cultured cells, and an animal model of chronic oxidative deficits. Annals of the New York Academy of Sciences, 893(1), 79-94.

Goedert, M., and Spillantini, M. G. (2006). A century of Alzheimer's disease. Science, 314(5800), 777-781.

Goez, M. M., Torres-Madroñero, M. C., Röthlisberger, S., and Delgado-Trejos, E. (2018). Preprocessing of 2-dimensional gel electrophoresis images applied to proteomic analysis: a review. Genomics, proteomics and bioinformatics, 16(1), 63-72.

Gong, C.-X., Grundke-Iqbal, I., and Iqbal, K. (1994). Dephosphorylation of Alzheimer's disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience, 61(4), 765-772.

Graves, P. R., and Haystead, T. A. (2002). Molecular biologist's guide to proteomics. Microbiology and Molecular Biology Reviews, 66(1), 39-63.

Guo, H., Albrecht, S., Bourdeau, M., Petzke, T., Bergeron, C., & LeBlanc, A. C. (2004). Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. The American journal of pathology, 165(2), 523-531.

Kapasi, A., DeCarli, C., and Schneider, J. A. (2017). Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathologica, 134(2), 171-186.

Khachaturian, Z. S. (1985). Diagnosis of Alzheimer's disease. Archives of Neurology, 42(11), 1097-1105.

Liao, L., Cheng, D., Wang, J., Duong, D. M., Losik, T. G., Gearing, M., and Peng, J. (2004). Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. Journal of Biological Chemistry, 279(35), 37061-37068.

Lista, S., Zetterberg, H., Dubois, B., Blennow, K., and Hampel, H. (2014). Cerebrospinal fluid analysis in Alzheimer’s disease: technical issues and future developments. Journal of Neurology, 261(6), 1234-1243.

Malia, T. J., Teplyakov, A., Ernst, R., Wu, S. J., Lacy, E. R., Liu, X., and Sweet, R. W. (2016). Epitope mapping and structural basis for the recognition of phosphorylated tau by the anti‐tau antibody AT8. Proteins: Structure, Function, and Bioinformatics, 84(4), 427-434.

Marcus, K., Lelong, C., and Rabilloud, T. (2020). What Room for Two-Dimensional Gel-Based Proteomics in a Shotgun Proteomics World? Proteomes, 8(3), 17.

McKetney, J., Runde, R. M., Hebert, A. S., Salamat, S., Roy, S., and Coon, J. J. (2019). Proteomic atlas of the human brain in alzheimer’s disease. Journal of proteome research, 18(3), 1380-1391.

Mucke, L. (2009). Alzheimer's disease. Nature, 461(7266), 895-897.

Ondrejcak, T., Klyubin, I., Corbett, G. T., Fraser, G., Hong, W., Mably, A. J., Gardener. M., Hammersley. J., Perkinton. M. S., Billinton, A., Walsh. D. M., and Rowan. M. J. (2018). Cellular prion protein mediates the disruption of hippocampal synaptic plasticity by soluble tau in vivo. Journal of Neuroscience, 38(50), 10595-10606.

Papasozomenos, S. C., & Su, Y. (1991). Altered phosphorylation of tau protein in heat-shocked rats and patients with Alzheimer disease. Proceedings of the National Academy of Sciences, 88(10), 4543-4547.

Paterson, R., Heywood, W., Heslegrave, A., Magdalinou, N., Andreasson, U., Sirka, E., Bliss. E., Slattery. C. F., Toobs. J., Svensson. J., Johansson. P., Fox. C. N., Zetterberg. H., Mills. K., and Schott. J. M. (2016). A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer’s disease pathology. Translational psychiatry, 6(11), e952-e952.

Riudavets, M. A., Iacono, D., Resnick, S. M., O’Brien, R., Zonderman, A. B., Martin, L. J., Rudow. G., Pletnikova. O., and Troncoso, J. C. (2007). Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons. Neurobiology of Aging, 28(10), 1484-1492.

Rudrabhatla, P., Jaffe, H., and Pant, H. C. (2011). Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. The FASEB Journal, 25(11), 3896-3905.

Serrano-Pozo, A., Frosch, M. P., Masliah, E., and Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 1(1), a006189.

Soares, H. D., Chen, Y., Sabbagh, M., Rohrer, A., Schrijvers, E., and Breteler, M. (2009). Identifying early markers of Alzheimer's disease using quantitative multiplex proteomic immunoassay panels. Annals of the New York Academy of Sciences, 1180(1), 56-67.

Stokes, M., and Trickey, R. (1973). Screening for neurofibrillary tangles and argyrophilic plaques with Congo Red and polarized light. Journal of clinical pathology, 26(3), 241.

Szendrei, G., Lee, V. Y., and Otvos Jr, L. (1993). Recognition of the minimal epitope of monoclonal antibody Tau‐1 depends upon the presence of a phosphate group but not its location. Journal of neuroscience research, 34(2), 243-249.

Takashima, A., Murayama, M., Yasutake, K., Takahashi, H., Yokoyama, M., and Ishiguro, K. (2001). Involvement of cyclin dependent kinase5 activator p25 on tau phosphorylation in mouse brain. Neuroscience letters, 306(1-2), 37-40.

Townsend, M., Shankar, G. M., Mehta, T., Walsh, D. M., and Selkoe, D. J. (2006). Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers. The Journal of physiology, 572(2), 477-492.

Valledor, L., and Jorrín, J. (2011). Back to the basics: maximizing the information obtained by quantitative two-dimensional gel electrophoresis analyses by an appropriate experimental design and statistical analyses. Journal of Proteomics, 74(1), 1-18.

Walji, A. M., Hostetler, E. D., Selnick, H., Zeng, Z., Miller, P., Bennacef, I., Salinas. C., Connolly. B., Gantert. L., Holahan. M., O’Malley. S., Purcell. M., Riffel. K., Li. J., Balsells. J., Brien. J. A. O., Melquist. S., Soriano. A., Zhang. X., Ogawa. A., Xu. S., Joshi. E., Rocca. J. D., Hess. F.J., Schacter. S., Hesk. D., Schenk. D., Struyk. A., Babaoglu. K., Lohith. T.G., Wang. Y., Yang. K., Fu. J., Evelhoch. J. L., and Coleman. P. J. (2016). Discovery of 6-(Fluoro-18 F)-3-(1 H-pyrrolo [2, 3-c] pyridin-1-yl) isoquinolin-5-amine ([18F]-MK-6240): A positron emission tomography (PET) imaging agent for quantification of neurofibrillary tangles (NFTs). Journal of Medicinal Chemistry, 59(10), 4778-4789.

Wang, H., Yang, J., Schneider, J. A., De Jager, P. L., Bennett, D. A., and Zhang, H.-Y. (2020). Genome-wide interaction analysis of pathological hallmarks in Alzheimer's disease. Neurobiology of aging, 93, 61-68.

Washburn, M. P., Wolters, D., and Yates, J. R. (2001). Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nature biotechnology, 19(3), 242-247.

Wenk, G. L. (2003). Neuropathologic changes in Alzheimer's disease. Journal of Clinical Psychiatry, 64, 7-10.

Whiteman, M., Cheung, N. S., Zhu, Y.-Z., Chu, S. H., Siau, J. L., Wong, B. S., Armstrong. J. S., and Moore, P. K. (2005). Hydrogen sulphide: a novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain? Biochemical and biophysical research communications, 326(4), 794-798.

Xu, J., Patassini, S., Rustogi, N., Riba-Garcia, I., Hale, B. D., Phillips, A. M., Waldvogel., H., Haines. R., Bradbury. P., Stevens. A., Faull. R. L., M., Dowsey. A. W., Cooper. G. J. S., and Stevens, A. (2019). Regional protein expression in human Alzheimer’s brain correlates with disease severity. Communications Biology, 2(1), 1-15.

Yamamoto, T., and Hirano, A. (1986). A comparative study of modified Bielschowsky, Bodian and thioflavin S stains on Alzheimer's neurofibrillary tangles. Neuropathology and Applied Neurobiology, 12(1), 3-9.

Zabel, M., Nackenoff, A., Kirsch, W. M., Harrison, F. E., Perry, G., and Schrag, M. (2018). Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: a meta-analysis in human pathological specimens. Free Radical Biology and Medicine, 115, 351-360.

DOI: https://doi.org/10.17509/ajse.v2i3.39391


  • There are currently no refbacks.

Copyright (c) 1970 Universitas Pendidikan Indonesia

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

ASEAN Journal of Science and Engineering (AJSE) is published by UPI 

View My Stats