Biomarkers for Alzheimer's Disease Diagnosis

Author(s): Vasileios Mantzavinos, Athanasios Alexiou*

Journal Name: Current Alzheimer Research

Volume 14 , Issue 11 , 2017

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Abstract:

Objective: The dramatic increase in the population with dementia expected in the next decades is accompanied by the establishment of novel and innovated methods that will offer accurate and efficient detection of the disease in its early stages. While Alzheimer's disease is the most common cause of dementia, by the time it is typically diagnosed, substantial neuronal loss and neuropathological lesions can damage many brain regions. The aim of this study is to investigate the main risk factors that affect and increase Alzheimer's disease progression over time even in cases with no significant memory impairment present. Several potential markers are discussed such as oxidative stress, metal ions, vascular disorders, protein dysfunctions and alterations in the mitochondrial populations.

Conclusion: A multiparametric model of Alzheimer's biomarkers is presented according to the latest classification of the disease.

Keywords: Alzheimer's disease biomarkers, oxidative stress, metal ions, vascular disorders, protein dysfunctions, mitochondrial dynamics, mild cognitive impairment.

[1]
Kukull WA, Bowen JD. Dementia epidemiology. Med Clin North Am 86: 573-90. (2002).
[2]
DeKosky ST, Marek K. Looking backward to move forward: early detection of neurodegenerative disorders. Science 302: 830-4. (2003).
[3]
Dickerson BC, Salat DH, Greve DN, Chua EF, Rand-Giovannetti E, Rentz DM, et al. Sperling RA increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65(3): 404-11. (2005).
[4]
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, et al. Scheltens P research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6(8): 734-46. (2007).
[5]
Dickerson BC, Sperling RA. Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer’s disease: insights from functional MRI studies. Neuropsychologia 46(6): 1624-35. (2008).
[6]
Alexiou A, Rekkas J, Vlamos P. Modeling the mitochondrial dysfunction in neurogenerative diseases due to high H+ concentration. Bioinformation 6(5): 173-5. (2011).
[7]
Alexiou A, Rekkas J. Superconductivity in Human Body; Myth or Necessity. Springer International Publishing Switzerland 2015. In (Eds: Vlamos P, Alexiou A). From Advances in Experimental Medicine and Biology pp 822. GeNeDis 2014 (2014).
[8]
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging and Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer’s Demen 7(3): 270-9. (2011).
[9]
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. Mild cognitive impairment (MCI) due to Alzheimers Disease Workgroup. Curr Med Chem Immunol Endocr Metab Agents 3: 371-83. (2010).
[10]
Ringman JM, Liang LJ, Zhou Y, Vangala S, Teng E, Kremen S, et al. Early behavioural changes in familial Alzheimer’s disease in the dominantly inherited alzheimer network. Brain 138(4): 1036-45. (2015).
[11]
Choi EJ, Bang H, Im JH, Chung SJ. Lee JH. A case of biopsy-proven early-onset Alzheimer’s disease with hemiparkinsonism. J Clin Neurol 1(1): 97-100. (2005).
[12]
Biomarkers across neurodegenerative diseases. Available from http://www.alz.org/research/alzheimers_grants/biomarkers-across.asp
[13]
Mohs RC, Haroutunian V. Alzheimer disease: from earliest symptoms to end stage. In (Eds: Davis KL, Charney D, Coyle JT, and Nemeroff C). Alzheimer disease: from earliest symptoms to end stage. Neuropsychopharmacology: The Fifth Generation of Progress. Am Coll Νeuropsychopharmacol 82: 1189-97 (2002).
[14]
Sutphen CL, Jasielec MS, Shah AR, Macy EM, Xiong C, Vlassenko AG, et al. Longitudinal cerebrospinal fluid biomarker changes in preclinical Alzheimer disease during middle age. JAMA Neurol 72(9): 1029-42. (2015).
[15]
Davis KL, Mohs RC, Marin D, Purohit DP, Perl DP, Lantz M, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA 281(15): 1401-6. (1999).
[16]
Arendash GW, Gordon MN, Diamond DM, Austin LA, Hatcher JM, Jantzen P, et al. Behavioral assessment of Alzheimer’s transgenic mice following long-term ab vaccination: task specificity and correlations between ab deposition and spatial memory. DNA Cell Biol 20: 737-44. (2001).
[17]
Howlett DR. Protein misfolding in disease: cause or response? Curr Med Chem Immunol Endocr Metab Agents 3(4): 371-83. (2003).
[18]
Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, et al. Alzheimer’s disease amyloid-b links lens and brain pathology in down syndrome. Plos One 5(5)e10659 (2010).
[19]
Mentenopoulos G, Mpouras K. Eds. The disease of Alzheimer. University Studio Press, (2002).
[20]
Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FRJ, et al. the Amyloid Biomarker Study Group. Prevalence of cerebral amyloid pathology in persons without dementia. JAMA 313(19): 1924-38. (2015).
[21]
Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, Wiesje M. van der Flier Bart NM, et al, and the Amyloid PET Study Group. Prevalence of amyloid pet positivity in dementia syndromes a meta-analysis. JAMA 313(19): 1939-50 (2015).
[22]
Buée L, Bussière T, Buée-Scherrer V, Delacourte A. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33(1): 95-130. (2000).
[23]
Nazem A, Mansoori GA. Nanotechnology for Alzheimer’s disease detection and treatment. Insciences J 1(4): 169-93. (2011).
[24]
Chan DC. Mitochondrial dynamics in disease. N Engl J Med 356(17): 1707-9. (2007).
[25]
Besson FL, La Joie R, Doeuvre L, Gaubert M, Mézenge F, Egret S, et al. Cognitive and brain profiles associated with current neuroimaging biomarkers of preclinical Alzheimer’s disease. J Neurosci 35(29): 10402-11. (2015).
[26]
Thordardottir S, Ståhlbom AK, Ferreira D, Almkvist O, Westman E, Zetterberg H, et al. Preclinical cerebrospinal fluid and volumetric magnetic resonance imaging biomarkers in Swedish familial Alzheimer’s disease. J Alzheimers Dis 43(4): 1393-02. (2015).
[27]
Risacher SL, Kim S, Nho K, Foroud T, Shen L, Petersen RC, et al. APOE effect on Alzheimer’s disease biomarkers in older adults with significant memory concern. Alzheimers Dement 11(12): 1417-29. (2015).
[28]
Cauwenberghe CV, Broeckhoven CV. Sleegers DSc, Sleegers K. The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 18(5): 421-30. (2016).
[29]
Michel G. Alzheimer’s and Parkinson’s diseases: the prion concept in relation to assembled Aβ, tau, and α-synuclein. Science 349(6248)1255555 (2015).
[30]
Wang X, Su B, Lee H, Xinyi Li, Perry G, Smith MA, et al. Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29(28): 9090-103. (2009).
[31]
Cabezas-Opazo FA, Vergara-Pulgar K, Pérez MJ, Jara C, Osorio-Fuentealba C, Quintanilla RA. Mitochondrial dysfunction contributes to the pathogenesis of alzheimer’s disease. Oxid Med Cell Longev 2015: 509654 (2015).
[32]
Gaël N, Wallon D, Charbonnier C, Quenez O, Rousseau S, Richard AC, et al. Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet 24(5): 710-6. (2016).
[33]
Quiroz YT, Schultz AP, Chen K, Protas HD, Brickhouse M, Fleisher AS, et al. Brain imaging and blood biomarker abnormalities in children with autosomal dominant alzheimer disease: a cross-sectional study. JAMA Neurol 72(8): 912-9. (2015).
[34]
Schindler SE, Fagan AM. Autosomal dominant Alzheimer disease: a unique resource to study csf biomarker changes in preclinical ad. Front Neurol 6: 142. (2015).
[35]
Duce JA, Bush AI, Adlard PA. Role of Amyloid-β-metal interactions in Alzheimer’s disease. Future Neurol 6(5): 641-59. (2015).
[36]
Sastre M, Ritchie CW, Hajji N. Metal ions in Alzheimer’s disease brain. JSM Alzheimers Dis Relat Dement 2(1): 1014. (2015).
[37]
Hooper C, Meimaridou E, Tavassoli M, Melino G, Lovestone S, Killick R. p53 is upregulated in Alzheimer’s disease and induces tau phosphorylation in HEK293a cells. Neurosci Lett 418(1): 34-7. (2007).
[38]
Stanga S, Lanni C, Govoni S, Uberti D, D’Orazi G, Racchi M. Unfolded p53 in the pathogenesis of Alzheimer’s disease: is HIPK2 the link? Aging 2(9): 545-54. (2010).
[39]
Buizza L, Prandelli C, Bonini SA, Delbarba A, Cenini G, Lanni C, et al. Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression. Cell Death Dis 4e484 (2013).
[40]
Nakanishi A, Minami A, Kitagishi Y, Ogura Y, Matsuda S. BRCA1 and p53 tumor suppressor molecules in Alzheimer’s disease. Int J Mol Sci 16(2): 2879-92. (2015).
[41]
Madeira C, Lourenco MV, Vargas-Lopes C, Suemoto CK, Brandão CO, Reis T, et al. D-serine levels in Alzheimer’s disease: implications for novel biomarker development. Transl Psychiatry 5e561 (2015).
[42]
Dong H, Li J, Huang L, Chen X, Li D, Wang T, et al. Serum microrna profiles serve as novel biomarkers for the diagnosis of Alzheimer’s disease. Dis Markers 2015625659 (2015).
[43]
Skoog I, Gustafson D. Update on hypertension and Alzheimer’s disease. Neurol Res 28(6): 605-11. (2006).
[44]
Kennelly S, Collins O. Walking the cognitive “minefield” between high and low blood pressure. J Alzheimers Dis 32(3): 609-21. (2012).
[45]
Skoog I, Gustafson D. Hypertension, hypertension-clustering factors and Alzheimer’s disease. Neurol Res 25(6): 675-80. (2003).
[46]
Østergaard SD, Mukherjee S, Sharp SJ, Proitsi P, Lotta LA, Day F, et al. Associations between potentially modifiable risk factors and alzheimer disease: a mendelian randomization study. PLoS Med 12(6)e100184 (2015).
[47]
Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, et al. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 63(5): 665-72. (2006).
[48]
Grundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, et al. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol 61(1): 59-66. (2004).
[49]
Belmokhtar N, Benamrane N. Classification of Alzheimer’s disease from 3d structural mri data. Intern J Comp App 47(3): 40-4. (2012).
[50]
Yang Z, Wen W, Jiang J, Crawford JD, Reppermund S, Levitan C, et al. Structural MRI biomarkers of mild cognitive impairment from young elders to centenarians. Curr Alzheimer Res 13(3): 256-67. (2016).
[51]
Counts SE, He B, Prout JG, Michalski B, Farotti L, Fahnestock M, et al. Cerebrospinal fluid prongf: a putative biomarker for early alzheimer’s disease. Curr Alzheimer Res 13(7): 800-8. (2016).
[52]
Eskildsen SF, Coupé P, Fonov VS, Pruessner JC, Collins DL. Structural imaging biomarkers of Alzheimer’s disease: predicting disease progression. Neurobiol Aging 36(1): 23-31. (2015).
[53]
Corrado M, Scorrano L, Campello S. Mitochondrial dynamics in cancer and neurodegenerative and neuroinflammatory diseases, Hindawi Publishing Corporation. International J Cell Biol 2012. (2012).
[54]
Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al. Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21(9): 3017-23. (2001).
[55]
Martin LJ. Mitochondrial and cell death mechanisms in neurodegenerative diseases. Pharmaceuticals 3(4): 839-915. (2010).
[56]
Vlamos P, Alexiou A. Computational biology and bioinformatics. Springer Series: advances in experimental medicine and biology. In (Eds:Vlamos P, Alexiou A). World Congress on Geriatrics and Neurodegenerative Disease Research. Content level: Research (2015).
[57]
Vlamos P, Alexiou A. Geriatrics, Springer Series: advances in experimental medicine and biology. In (Eds: Vlamos P, Alexiou A). World Congress on Geriatrics and Neurodegenerative Disease Research, Content level: Research (2015).
[58]
Vlamos P, Alexiou A. Computational biology and bioinformatics, Springer Series: Advances in experimental medicine and biology. In (Eds: Vlamos P, Alexiou A). World congress on geriatrics and neurodegenerative disease research, content level: research (2015).


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Article Details

VOLUME: 14
ISSUE: 11
Year: 2017
Page: [1149 - 1154]
Pages: 6
DOI: 10.2174/1567205014666170203125942

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