Omics-based Biomarkers for the Early Alzheimer Disease Diagnosis and Reliable Therapeutic Targets Development

Author(s): Carmen Peña-Bautista, Miguel Baquero, Máximo Vento, Consuelo Cháfer-Pericás*

Journal Name: Current Neuropharmacology

Volume 17 , Issue 7 , 2019

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Graphical Abstract:


Background: Alzheimer’s disease (AD), the most common cause of dementia in adulthood, has great medical, social, and economic impact worldwide. Available treatments result in symptomatic relief, and most of them are indicated from the early stages of the disease. Therefore, there is an increasing body of research developing accurate and early diagnoses, as well as diseasemodifying therapies.

Objective: Advancing the knowledge of AD physiopathological mechanisms, improving early diagnosis and developing effective treatments from omics-based biomarkers.

Methods: Studies using omics technologies to detect early AD, were reviewed with a particular focus on the metabolites/lipids, micro-RNAs and proteins, which are identified as potential biomarkers in non-invasive samples.

Results: This review summarizes recent research on metabolomics/lipidomics, epigenomics and proteomics, applied to early AD detection. Main research lines are the study of metabolites from pathways, such as lipid, amino acid and neurotransmitter metabolisms, cholesterol biosynthesis, and Krebs and urea cycles. In addition, some microRNAs and proteins (microglobulins, interleukins), related to a common network with amyloid precursor protein and tau, have been also identified as potential biomarkers. Nevertheless, the reproducibility of results among studies is not good enough and a standard methodological approach is needed in order to obtain accurate information.

Conclusion: The assessment of metabolomic/lipidomic, epigenomic and proteomic changes associated with AD to identify early biomarkers in non-invasive samples from well-defined participants groups will potentially allow the advancement in the early diagnosis and improvement of therapeutic interventions.

Keywords: Metabolomics, lipidomics, epigenomics, proteomics, Alzheimer disease, biomarkers, mild cognitive impairment.

Duckett, L. Alzheimer’s dementia: morbidity and mortality. J. Insur. Med., 2001, 33(3), 227-234. [PMID: 11558402].
Qiu, C.; Kivipelto, M.; von Strauss, E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin. Neurosci., 2009, 11(2), 111-128. [PMID: 19585947].
[3] 2008.
Brookmeyer, R.; Johnson, E.; Ziegler-Graham, K.; Arrighi, H.M. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement., 2007, 3(3), 186-191. []. [PMID: 19595937].
Herrmann, N.; Chau, S.A.; Kircanski, I.; Lanctôt, K.L. Current and emerging drug treatment options for Alzheimer’s disease: a systematic review. Drugs, 2011, 71(15), 2031-2065. []. [PMID: 21985169].
Visser, P.J.; Vos, S.; van Rossum, I.; Scheltens, P. Comparison of International Working Group criteria and National Institute on Aging-Alzheimer’s Association criteria for Alzheimer’s disease. Alzheimers Dement., 2012, 8(6), 560-563. []. [PMID: 23102126].
Bertens, D.; Knol, D.L.; Scheltens, P.; Visser, P.J. Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer’s disease. Alzheimers Dement., 2015, 11(5), 511-522. []. [PMID: 25150730].
Albert, M.S.; DeKosky, S.T.; Dickson, D.; Dubois, B.; Feldman, H.H.; Fox, N.C.; Gamst, A.; Holtzman, D.M.; Jagust, W.J.; Petersen, R.C.; Snyder, P.J.; Carrillo, M.C.; Thies, B.; Phelps, C.H. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement., 2011, 7(3), 270-279. []. [PMID: 21514249].
McKhann, G.M.; Knopman, D.S.; Chertkow, H.; Hyman, B.T.; Jack, C.R., Jr; Kawas, C.H.; Klunk, W.E.; Koroshetz, W.J.; Manly, J.J.; Mayeux, R.; Mohs, R.C.; Morris, J.C.; Rossor, M.N.; Scheltens, P.; Carrillo, M.C.; Thies, B.; Weintraub, S.; Phelps, C.H. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement., 2011, 7(3), 263-269. []. [PMID: 21514250].
Hughes, C.P.; Berg, L.; Danziger, W.L.; Coben, L.A.; Martin, R.L. A new clinical scale for the staging of dementia. Br. J. Psychiatry, 1982, 140, 566-572. []. [PMID: 7104545].
Reisberg, B.; Ferris, S.H.; de Leon, M.J.; Crook, T. The Global Deterioration Scale for assessment of primary degenerative dementia. Am. J. Psychiatry, 1982, 139(9), 1136-1139. []. [PMID: 7114305].
Moretti, D.V. Mild cognitive impairment: structural, metabolical, and neurophysiological evidence of a novel EEG biomarker. Front. Neurol., 2015, 6, 152. []. [PMID: 26217299].
Lista, S.; O’Bryant, S.E.; Blennow, K.; Dubois, B.; Hugon, J.; Zetterberg, H.; Hampel, H. Biomarkers in Sporadic and Familial Alzheimer’s Disease. J. Alzheimers Dis., 2015, 47(2), 291-317. []. [PMID: 26401553].
Terry, R.D. Cell death or synaptic loss in Alzheimer disease. J. Neuropathol. Exp. Neurol., 2000, 59(12), 1118-1119. []. [PMID: 11138931].
Mohamed, A.; Cortez, L.; de Chaves, E.P. Aggregation state and neurotoxic properties of alzheimer β-amyloid peptide. Curr. Protein Pept. Sci., 2011, 12(3), 235-257. []. [PMID: 21348837].
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70. []. [PMID: 28872215].
Le Page, A.; Dupuis, G.; Frost, E.H.; Larbi, A.; Pawelec, G.; Witkowski, J.M.; Fulop, T. Role of the peripheral innate immune system in the development of Alzheimer's disease. Exp. Gerontol.,, 2017. S0531-5565, 30541-30547.
Pimplikar, S.W. Multi-omics and Alzheimer’s disease: a slower but surer path to an efficacious therapy? Am. J. Physiol. Cell Physiol., 2017, 313(1), C1-C2. []. [PMID: 28515086].
Zetterberg, H. Applying fluid biomarkers to Alzheimer’s disease. Am. J. Physiol. Cell Physiol., 2017, 313(1), C3-C10. []. [PMID: 28424166].
Patti, G.J.; Yanes, O.; Siuzdak, G. Innovation: Metabolomics: the apogee of the omics trilogy. Nat. Rev. Mol. Cell Biol., 2012, 13(4), 263-269. []. [PMID: 22436749].
Pan, X.; Nasaruddin, M.B.; Elliott, C.T.; McGuinness, B.; Passmore, A.P.; Kehoe, P.G.; Hölscher, C.; McClean, P.L.; Graham, S.F.; Green, B.D. Alzheimer’s disease-like pathology has transient effects on the brain and blood metabolome. Neurobiol. Aging, 2016, 38, 151-163. []. [PMID: 26827653].
Wang, G.; Zhou, Y.; Huang, F.J.; Tang, H.D.; Xu, X.H.; Liu, J.J.; Wang, Y.; Deng, Y.L.; Ren, R.J.; Xu, W.; Ma, J.F.; Zhang, Y.N.; Zhao, A.H.; Chen, S.D.; Jia, W. Plasma metabolite profiles of Alzheimer’s disease and mild cognitive impairment. J. Proteome Res., 2014, 13(5), 2649-2658. []. [PMID: 24694177].
Han, X.; Rozen, S.; Boyle, S.H.; Hellegers, C.; Cheng, H.; Burke, J.R.; Welsh-Bohmer, K.A.; Doraiswamy, P.M.; Kaddurah-Daouk, R. Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS One, 2011, 6(7)e21643 []. [PMID: 21779331].
Yu, L.; Chibnik, L.B.; Srivastava, G.P.; Pochet, N.; Yang, J.; Xu, J.; Kozubek, J.; Obholzer, N.; Leurgans, S.E.; Schneider, J.A.; Meissner, A.; De Jager, P.L.; Bennett, D.A. Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease. JAMA Neurol., 2015, 72(1), 15-24. []. [PMID: 25365775].
Pan, Y.; Liu, R.; Terpstra, E.; Wang, Y.; Qiao, F.; Wang, J.; Tong, Y.; Pan, B. Dysregulation and diagnostic potential of microRNA in Alzheimer’s disease. J. Alzheimers Dis., 2016, 49(1), 1-12. []. [PMID: 26484912].
Yılmaz, Ş.G.; Erdal, M.E.; Özge, A.A.; Sungur, M.A. Can Peripheral MicroRNA Expression Data Serve as Epigenomic (Upstream) Biomarkers of Alzheimer’s Disease? OMICS, 2016, 20(8), 456-461. []. [PMID: 27501295].
Cheng, L.; Quek, C.Y.; Sun, X.; Bellingham, S.A.; Hill, A.F. The detection of microRNA associated with Alzheimer’s disease in biological fluids using next-generation sequencing technologies. Front. Genet., 2013, 4, 150. []. [PMID: 23964286].
Wyss-Coray, T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med., 2006, 12(9), 1005-1015. [PMID: 16960575].
Ray, S.; Britschgi, M.; Herbert, C.; Takeda-Uchimura, Y.; Boxer, A.; Blennow, K.; Friedman, L.F.; Galasko, D.R.; Jutel, M.; Karydas, A.; Kaye, J.A.; Leszek, J.; Miller, B.L.; Minthon, L.; Quinn, J.F.; Rabinovici, G.D.; Robinson, W.H.; Sabbagh, M.N.; So, Y.T.; Sparks, D.L.; Tabaton, M.; Tinklenberg, J.; Yesavage, J.A.; Tibshirani, R.; Wyss-Coray, T. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat. Med., 2007, 13(11), 1359-1362. []. [PMID: 17934472].
Guo, L.H.; Alexopoulos, P.; Wagenpfeil, S.; Kurz, A.; Perneczky, R. Plasma proteomics for the identification of Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2013, 27(4), 337-342. []. [PMID: 23314060].
Petersen, R.C.; Smith, G.E.; Waring, S.C.; Ivnik, R.J.; Kokmen, E.; Tangelos, E.G. Aging, memory, and mild cognitive impairment. Int. Psychogeriatr., 1997, 9(Suppl. 1), 65-69. []. [PMID: 9447429].
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 1984, 34(7), 939-944. []. [PMID: 6610841].
González-Domínguez, R.; Rupérez, F.J.; García-Barrera, T.; Barbas, C.; Gómez-Ariza, J.L. Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer’s Disease and Mild Cognitive Impairment. Curr. Alzheimer Res., 2016, 13(6), 641-653. []. [PMID: 26825096].
González-Domínguez, R.; García, A.; García-Barrera, T.; Barbas, C.; Gómez-Ariza, J.L. Metabolomic profiling of serum in the progression of Alzheimer’s disease by capillary electrophoresis-mass spectrometry. Electrophoresis, 2014, 35(23), 3321-3330. []. [PMID: 25136972].
Graham, S.F.; Chevallier, O.P.; Elliott, C.T.; Hölscher, C.; Johnston, J.; McGuinness, B.; Kehoe, P.G.; Passmore, A.P.; Green, B.D. Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer’s disease. PLoS One, 2015, 10(3)e0119452 []. [PMID: 25803028].
Mapstone, M.; Lin, F.; Nalls, M.A.; Cheema, A.K.; Singleton, A.B.; Fiandaca, M.S.; Federoff, H.J. What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessons for Alzheimer’s disease. Neurobiol. Aging, 2017, 51, 148-155. []. [PMID: 27939698].
de Leeuw, F.A.; Peeters, C.F.W.; Kester, M.I.; Harms, A.C.; Struys, E.A.; Hankemeier, T.; van Vlijmen, H.W.T.; van der Lee, S.J.; van Duijn, C.M.; Scheltens, P.; Demirkan, A.; van de Wiel, M.A.; van der Flier, W.M.; Teunissen, C.E. Blood-based metabolic signatures in Alzheimer’s disease. Alzheimers Dement. (Amst.), 2017, 8, 196-207. []. [PMID: 28951883].
Olazarán, J.; Gil-de-Gómez, L.; Rodríguez-Martín, A.; Valentí-Soler, M.; Frades-Payo, B.; Marín-Muñoz, J.; Antúnez, C.; Frank-García, A.; Acedo-Jiménez, C.; Morlán-Gracia, L.; Petidier-Torregrossa, R.; Guisasola, M.C.; Bermejo-Pareja, F.; Sánchez-Ferro, Á.; Pérez-Martínez, D.A.; Manzano-Palomo, S.; Farquhar, R.; Rábano, A.; Calero, M. A blood-based, 7-metabolite signature for the early diagnosis of Alzheimer’s disease. J. Alzheimers Dis., 2015, 45(4), 1157-1173. []. [PMID: 25649659].
Toledo, J.B.; Arnold, M.; Kastenmüller, G.; Chang, R.; Baillie, R.A.; Han, X.; Thambisetty, M.; Tenenbaum, J.D.; Suhre, K.; Thompson, J.W.; John-Williams, L.S.; Mahmoudian, D.S.; Rotroff, D.M.; Jack, J.R.; Motsinger-Reif, A.; Risacher, S.L.; Blach, C.; Lucas, J.E.; Massaro, T.; Louie, G.; Zhu, H.; Dallmann, G.; Klavins, K.; Koal, T.; Kim, S.; Nho, K.; Shen, L.; Casanova, R.; Varma, S.; Legido-Quigley, C.; Moseley, M.A.; Zhu, K.; Henrion, M.Y.R.; van der Lee, S.J.; Harms, A.C.; Demirkan, A.; Hankemeier, T.
van Duijn, C.M.; Trojanowski, J.Q.; Shaw, L.M.; Saykin, A.J.; Weiner, M.W.; Doraiswamy, P.M.; Kaddurah-Daouk, R. Metabolic network failures in Alzheimer’s disease: A biochemical road map. Alzheimers Dement., 2017, 13(9), 965-984. []. [PMID: 28341160].
Chouraki, V.; Preis, S.R.; Yang, Q.; Beiser, A.; Li, S.; Larson, M.G.; Weinstein, G.; Wang, T.J.; Gerszten, R.E.; Vasan, R.S.; Seshadri, S. Association of amine biomarkers with incident dementia and Alzheimer’s disease in the Framingham Study. Alzheimers Dement., 2017, 13(12), 1327-1336. []. [PMID: 28602601].
Orešič, M.; Anderson, G.; Mattila, I.; Manoucheri, M.; Soininen, H.; Hyötyläinen, T.; Basignani, C. Targeted Serum Metabolite Profiling Identifies Metabolic Signatures in Patients with Alzheimer’s Disease, Normal Pressure Hydrocephalus and Brain Tumor. Front. Neurosci., 2018, 11, 747. []. [PMID: 29375291].
Oberacher, H.; Arnhard, K.; Linhart, C.; Diwo, A.; Marksteiner, J.; Humpel, C. Targeted Metabolomic Analysis of Soluble Lysates from Platelets of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Compared to Healthy Controls: Is PC aeC40:4 a Promising Diagnostic Tool? J. Alzheimers Dis., 2017, 57(2), 493-504. []. [PMID: 28269764].
Liu, Y.; Li, N.; Zhou, L.; Li, Q.; Li, W. Plasma metabolic profiling of mild cognitive impairment and Alzheimer’s disease using liquid chromatography/mass spectrometry. Cent. Nerv. Syst. Agents Med. Chem., 2014, 14(2), 113-120. []. [PMID: 25515716].
Li, D.; Misialek, J.R.; Boerwinkle, E.; Gottesman, R.F.; Sharrett, A.R.; Mosley, T.H.; Coresh, J.; Wruck, L.M.; Knopman, D.S.; Alonso, A. Plasma phospholipids and prevalence of mild cognitive impairment and/or dementia in the ARIC Neurocognitive Study (ARIC-NCS). Alzheimers Dement. (Amst.), 2016, 3, 73-82. []. [PMID: 27408938].
Whiley, L.; Sen, A.; Heaton, J.; Proitsi, P.; García-Gómez, D.; Leung, R.; Smith, N.; Thambisetty, M.; Kloszewska, I.; Mecocci, P.; Soininen, H.; Tsolaki, M.; Vellas, B.; Lovestone, S.; Legido-Quigley, C. Evidence of altered phosphatidylcholine metabolism in Alzheimer’s disease. Neurobiol. Aging, 2014, 35(2), 271-278. []. [PMID: 24041970].
Simpson, B.N.; Kim, M.; Chuang, Y.F.; Beason-Held, L.; Kitner-Triolo, M.; Kraut, M.; Lirette, S.T.; Windham, B.G.; Griswold, M.E.; Legido-Quigley, C.; Thambisetty, M. Blood metabolite markers of cognitive performance and brain function in aging. J. Cereb. Blood Flow Metab., 2016, 36(7), 1212-1223. []. [PMID: 26661209].
Li, D.; Misialek, J.R.; Boerwinkle, E.; Gottesman, R.F.; Sharrett, A.R.; Mosley, T.H.; Coresh, J.; Wruck, L.M.; Knopman, D.S.; Alonso, A. Prospective associations of plasma phospholipids and mild cognitive impairment/dementia among African Americans in the ARIC Neurocognitive Study. Alzheimers Dement. (Amst.), 2016, 6, 1-10. []. [PMID: 28054030].
Iuliano, L.; Pacelli, A.; Ciacciarelli, M.; Zerbinati, C.; Fagioli, S.; Piras, F.; Orfei, M.D.; Bossù, P.; Pazzelli, F.; Serviddio, G.; Caltagirone, C.; Spalletta, G. Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer’s disease. J. Alzheimers Dis., 2013, 36(3), 545-553. []. [PMID: 23635405].
Proitsi, P.; Kim, M.; Whiley, L.; Simmons, A.; Sattlecker, M.; Velayudhan, L.; Lupton, M.K.; Soininen, H.; Kloszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Lovestone, S.; Powell, J.F.; Dobson, R.J.; Legido-Quigley, C. Association of blood lipids with Alzheimer’s disease: A comprehensive lipidomics analysis. Alzheimers Dement., 2017, 13(2), 140-151. []. [PMID: 27693183].
Proitsi, P.; Kim, M.; Whiley, L.; Pritchard, M.; Leung, R.; Soininen, H.; Kloszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Sham, P.; Lovestone, S.; Powell, J.F.; Dobson, R.J.; Legido-Quigley, C. Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer’s disease. Transl. Psychiatry, 2015. 5e494 [] [PMID: 25585166]
Ciavardelli, D.; Piras, F.; Consalvo, A.; Rossi, C.; Zucchelli, M.; Di Ilio, C.; Frazzini, V.; Caltagirone, C.; Spalletta, G.; Sensi, S.L. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer’s disease subjects. Neurobiol. Aging, 2016, 43, 1-12. []. [PMID: 27255810].
Savica, R.; Murray, M.E.; Persson, X.M.; Kantarci, K.; Parisi, J.E.; Dickson, D.W.; Petersen, R.C.; Ferman, T.J.; Boeve, B.F.; Mielke, M.M. Plasma sphingolipid changes with autopsy-confirmed Lewy Body or Alzheimer’s pathology. Alzheimers Dement. (Amst.), 2016, 3, 43-50. []. [PMID: 27152320].
Klavins, K.; Koal, T.; Dallmann, G.; Marksteiner, J.; Kemmler, G.; Humpel, C. The ratio of phosphatidylcholines to lysophosphatidylcholines in plasma differentiates healthy controls from patients with Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement. (Amst.), 2015, 1(3), 295-302. []. [PMID: 26744734].
Wood, P.L.; Locke, V.A.; Herling, P.; Passaro, A.; Vigna, G.B.; Volpato, S.; Valacchi, G.; Cervellati, C.; Zuliani, G. Targeted lipidomics distinguishes patient subgroups in mild cognitive impairment (MCI) and late onset Alzheimer’s disease (LOAD). BBA Clin., 2015, 5, 25-28. []. [PMID: 27051586].
Yilmaz, A.; Geddes, T.; Han, B.; Bahado-Singh, R.O.; Wilson, G.D.; Imam, K.; Maddens, M.; Graham, S.F. Diagnostic Biomarkers of Alzheimer’s Disease as Identified in Saliva using 1H NMR-Based Metabolomics. J. Alzheimers Dis., 2017, 58(2), 355-359. []. [PMID: 28453477].
Cháfer-Pericás, C.; Rahkonen, L.; Sánchez-Illana, A.; Kuligowski, J.; Torres-Cuevas, I.; Cernada, M.; Cubells, E.; Nuñez-Ramiro, A.; Andersson, S.; Vento, M.; Escobar, J. Ultra high performance liquid chromatography coupled to tandem mass spectrometry determination of lipid peroxidation biomarkers in newborn serum samples. Anal. Chim. Acta, 2015, 886, 214-220. []. [PMID: 26320656].
Cháfer-Pericás, C.; Torres-Cuevas, I.; Sanchez-Illana, A.; Escobar, J.; Kuligowski, J.; Solberg, R.; Garberg, H.T.; Huun, M.U.; Saugstad, O.D.; Vento, M. Development of a reliable analytical method to determine lipid peroxidation biomarkers in newborn plasma samples. Talanta, 2016, 153, 152-157. []. [PMID: 27130102].
Escobar, J.; Sánchez-Illana, Á.; Kuligowski, J.; Torres-Cuevas, I.; Solberg, R.; Garberg, H.T.; Huun, M.U.; Saugstad, O.D.; Vento, M.; Cháfer-Pericás, C. Development of a reliable method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry to measure thiol-associated oxidative stress in whole blood samples. J. Pharm. Biomed. Anal., 2016, 123, 104-112. []. [PMID: 26895495].
García-Blanco, A.; Peña-Bautista, C.; Oger, C.; Vigor, C.; Galano, J.M.; Durand, T.; Martín-Ibáñez, N.; Baquero, M.; Vento, M.; Cháfer-Pericás, C. Reliable determination of new lipid peroxidation compounds as potential early Alzheimer Disease biomarkers. Talanta, 2018, 184, 193-201. []. [PMID: 29674032].
Peña-Bautista, C.; Vigor, C.; Galano, J.M.; Oger, C.; Durand, T.; Ferrer, I.; Cuevas, A.; López-Cuevas, R.; Baquero, M.; López-Nogueroles, M.; Vento, M.; Hervás, D.; García-Blanco, A.; Cháfer-Pericás, C. Plasma lipid peroxidation biomarkers for early and non-invasive Alzheimer Disease detection. Free Radic. Biol. Med., 2018, 124, 388-394. []. [PMID: 29969716].
García-Giménez, J.L.; Sanchis-Gomar, F.; Lippi, G.; Mena, S.; Ivars, D.; Gomez-Cabrera, M.C.; Viña, J.; Pallardó, F.V. Epigenetic biomarkers: A new perspective in laboratory diagnostics. Clin. Chim. Acta, 2012, 413(19-20), 1576-1582. []. [PMID: 22664147].
Taguchi, Y.H.; Murakami, Y. Universal disease biomarker: can a fixed set of blood microRNAs diagnose multiple diseases? BMC Res. Notes, 2014, 7, 581. []. [PMID: 25176111].
Dong, H.; Li, J.; Huang, L.; Chen, X.; Li, D.; Wang, T.; Hu, C.; Xu, J.; Zhang, C.; Zen, K.; Xiao, S.; Yan, Q.; Wang, C.; Zhang, C.Y. Serum MicroRNA Profiles Serve as Novel Biomarkers for the Diagnosis of Alzheimer’s Disease. Dis. Markers, 2015, 2015625659 []. [PMID: 26078483].
Satoh, J.; Kino, Y.; Niida, S. MicroRNA-Seq Data Analysis Pipeline to Identify Blood Biomarkers for Alzheimer’s Disease from Public Data. Biomark. Insights, 2015, 10, 21-31. []. [PMID: 25922570].
Nagaraj, S.; Laskowska-Kaszub, K.; Dębski, K.J.; Wojsiat, J.; Dąbrowski, M.; Gabryelewicz, T.; Kuźnicki, J.; Wojda, U. Profile of 6 microRNA in blood plasma distinguish early stage Alzheimer’s disease patients from non-demented subjects. Oncotarget, 2017, 8(10), 16122-16143. []. [PMID: 28179587].
Keller, A.; Backes, C.; Haas, J.; Leidinger, P.; Maetzler, W.; Deuschle, C.; Berg, D.; Ruschil, C.; Galata, V.; Ruprecht, K.; Stähler, C.; Würstle, M.; Sickert, D.; Gogol, M.; Meder, B.; Meese, E. Validating Alzheimer’s disease micro RNAs using next-generation sequencing. Alzheimers Dement., 2016, 12(5), 565-576. []. [PMID: 26806387].
Leidinger, P.; Backes, C.; Deutscher, S.; Schmitt, K.; Mueller, S.C.; Frese, K.; Haas, J.; Ruprecht, K.; Paul, F.; Stähler, C.; Lang, C.J.; Meder, B.; Bartfai, T.; Meese, E.; Keller, A. A blood based 12-miRNA signature of Alzheimer disease patients. Genome Biol., 2013, 14(7), R78. []. [PMID: 23895045].
Cheng, L.; Doecke, J.D.; Sharples, R.A.; Villemagne, V.L.; Fowler, C.J.; Rembach, A.; Martins, R.N.; Rowe, C.C.; Macaulay, S.L.; Masters, C.L.; Hill, A.F. Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol. Psychiatry, 2015, 20(10), 1188-1196. []. [PMID: 25349172].
Satoh, J.; Kino, Y.; Niida, S. MicroRNA-Seq Data Analysis Pipeline to Identify Blood Biomarkers for Alzheimer’s Disease from Public Data. Biomark. Insights, 2015, 10, 21-31. []. [PMID: 25922570].
Yang, T.T.; Liu, C.G.; Gao, S.C.; Zhang, Y.; Wang, P.C. The Serum Exosome Derived MicroRNA-135a, -193b, and -384 Were Potential Alzheimer’s Disease Biomarkers. Biomed. Environ. Sci., 2018, 31(2), 87-96. [PMID: 29606187].
Luo, Q.; Chen, Y. Long noncoding RNAs and Alzheimer’s disease. Clin. Interv. Aging, 2016, 11, 867-872. []. [PMID: 27418812].
Deng, Y.; Xiao, L.; Li, W.; Tian, M.; Feng, X.; Feng, H.; Hou, D. Plasma long noncoding RNA 51A as a stable biomarker of Alzheimer’s disease. Int. J. Clin. Exp. Pathol., 2017, 10, 4694-4699.
Duits, F.H.; Brinkmalm, G.; Teunissen, C.E.; Brinkmalm, A.; Scheltens, P.; Van der Flier, W.M.; Zetterberg, H.; Blennow, K. Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer’s disease. Alzheimers Res. Ther., 2018, 10(1), 5. []. [PMID: 29370833].
Kiddle, S.J.; Steves, C.J.; Mehta, M.; Simmons, A.; Xu, X.; Newhouse, S.; Sattlecker, M.; Ashton, N.J.; Bazenet, C.; Killick, R.; Adnan, J.; Westman, E.; Nelson, S.; Soininen, H.; Kloszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Curtis, C.; Breen, G.; Williams, S.C.; Lovestone, S.; Spector, T.D.; Dobson, R.J. Plasma protein biomarkers of Alzheimer’s disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes. Transl. Psychiatry, 2015. 5e584 [] [PMID: 26080319]
Shen, L.; Liao, L.; Chen, C.; Guo, Y.; Song, D.; Wang, Y.; Chen, Y.; Zhang, K.; Ying, M.; Li, S.; Liu, Q.; Ni, J. Proteomics Analysis of Blood Serums from Alzheimer’s Disease Patients Using iTRAQ Labeling Technology. J. Alzheimers Dis., 2017, 56(1), 361-378. []. [PMID: 27911324].
Cardoso, B.R.; Hare, D.J.; Bush, A.I.; Li, Q.X.; Fowler, C.J.; Masters, C.L.; Martins, R.N.; Ganio, K.; Lothian, A.; Mukherjee, S.; Kapp, E.A.; Roberts, B.R. Selenium Levels in Serum, Red Blood Cells, and Cerebrospinal Fluid of Alzheimer’s Disease Patients: A Report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). J. Alzheimers Dis., 2017, 57(1), 183-193. []. [PMID: 28222503].
Suzuki, I.; Noguchi, M.; Arito, M.; Sato, T.; Omoteyama, K.; Maedomari, M.; Hasegawa, H.; Suematsu, N.; Okamoto, K.; Kato, T.; Yamaguchi, N.; Kurokawa, M.S. Serum peptides as candidate biomarkers for dementia with Lewy bodies. Int. J. Geriatr. Psychiatry, 2015, 30(12), 1195-1206. []. [PMID: 25754375].
Muenchhoff, J.; Poljak, A.; Song, F.; Raftery, M.; Brodaty, H.; Duncan, M.; McEvoy, M.; Attia, J.; Schofield, P.W.; Sachdev, P.S. Plasma protein profiling of mild cognitive impairment and Alzheimer’s disease across two independent cohorts. J. Alzheimers Dis., 2015, 43(4), 1355-1373. []. [PMID: 25159666].
Kitamura, Y.; Usami, R.; Ichihara, S.; Kida, H.; Satoh, M.; Tomimoto, H.; Murata, M.; Oikawa, S. Plasma protein profiling for potential biomarkers in the early diagnosis of Alzheimer’s disease. Neurol. Res., 2017, 39(3), 231-238. []. [PMID: 28107809].
Marksteiner, J.; Imarhiagbe, D.; Defrancesco, M.; Deisenhammer, E.A.; Kemmler, G.; Humpel, C. Analysis of 27 vascular-related proteins reveals that NT-proBNP is a potential biomarker for Alzheimer’s disease and mild cognitive impairment: a pilot-study. Exp. Gerontol., 2014, 50, 114-121. []. [PMID: 24333505].
Sattlecker, M.; Kiddle, S.J.; Newhouse, S.; Proitsi, P.; Nelson, S.; Williams, S.; Johnston, C.; Killick, R.; Simmons, A.; Westman, E.; Hodges, A.; Soininen, H.; Kłoszewska, I.; Mecocci, P.; Tsolaki, M.; Vellas, B.; Lovestone, S.; Dobson, R.J. Alzheimer’s disease biomarker discovery using SOMAscan multiplexed protein technology. Alzheimers Dement., 2014, 10(6), 724-734. []. [PMID: 24768341].
Lundström, S.L.; Yang, H.; Lyutvinskiy, Y.; Rutishauser, D.; Herukka, S.K.; Soininen, H.; Zubarev, R.A. Blood plasma IgG Fc glycans are significantly altered in Alzheimer’s disease and progressive mild cognitive impairment. J. Alzheimers Dis., 2014, 38(3), 567-579. []. [PMID: 24028868].
Edwards, M.; Hall, J.; Williams, B.; Johnson, L.; O’Bryant, S. Molecular markers of amnestic mild cognitive impairment among Mexican Americans. J. Alzheimers Dis., 2016, 49(1), 221-228. []. [PMID: 26444793].
Villarreal, A.E.; O’Bryant, S.E.; Edwards, M.; Grajales, S.; Britton, G.B. Serum-based protein profiles of Alzheimer’s disease and mild cognitive impairment in elderly Hispanics. Neurodegener. Dis. Manag., 2016, 6(3), 203-213. []. [PMID: 27229914].
O’Bryant, S.E.; Lista, S.; Rissman, R.A.; Edwards, M.; Zhang, F.; Hall, J.; Zetterberg, H.; Lovestone, S.; Gupta, V.; Graff-Radford, N.; Martins, R.; Jeromin, A.; Waring, S.; Oh, E.; Kling, M.; Baker, L.D.; Hampel, H. Comparing biological markers of Alzheimer’s disease across blood fraction and platforms: Comparing apples to oranges. Alzheimers Dement. (Amst.), 2015, 3, 27-34. []. [PMID: 27019866].
Llano, D.A.; Devanarayan, V.; Simon, A.J. Evaluation of plasma proteomic data for Alzheimer disease state classification and for the prediction of progression from mild cognitive impairment to Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2013, 27(3), 233-243. []. [PMID: 23023094].
Korolev, I.O.; Symonds, L.L.; Bozoki, A.C. Predicting Progression from Mild Cognitive Impairment to Alzheimer’s Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification. PLoS One, 2016, 11(2)e0138866 []. [PMID: 26901338].
Yang, H.; Lyutvinskiy, Y.; Herukka, S.K.; Soininen, H.; Rutishauser, D.; Zubarev, R.A. Prognostic polypeptide blood plasma biomarkers of Alzheimer’s disease progression. J. Alzheimers Dis., 2014, 40(3), 659-666. []. [PMID: 24503613].
Nazeri, A.; Ganjgahi, H.; Roostaei, T.; Nichols, T.; Zarei, M. Imaging proteomics for diagnosis, monitoring and prediction of Alzheimer’s disease. Neuroimage, 2014, 102(Pt 2), 657-665. []. [PMID: 25173418].
Jammeh, E.; Zhao, P.; Carroll, C.; Pearson, S.; Ifeachor, E. Identification of blood biomarkers for use in point of care diagnosis tool for Alzheimer’s disease. Conf. Proc. IEEE Eng. Med. Biol. Soc., 2016, 2016, 2415-2418. []. [PMID: 28268812].
Zhao, X.; Lejnine, S.; Spond, J.; Zhang, C.; Ramaraj, T.C.; Holder, D.J.; Dai, H.; Weiner, R.; Laterza, O.F. A candidate plasma protein classifier to identify Alzheimer’s disease. J. Alzheimers Dis., 2015, 43(2), 549-563. []. [PMID: 25114072].
O’Bryant, S.E.; Edwards, M.; Johnson, L.; Hall, J.; Villarreal, A.E.; Britton, G.B.; Quiceno, M.; Cullum, C.M.; Graff-Radford, N.R. A blood screening test for Alzheimer’s disease. Alzheimers Dement. (Amst.), 2016, 3, 83-90. []. [PMID: 27453929].
Reumiller, C.M.; Schmidt, G.J.; Dhrami, I.; Umlauf, E.; Rappold, E.; Zellner, M. Gender-related increase of tropomyosin-1 abundance in platelets of Alzheimer’s disease and mild cognitive impairment patients. J. Proteomics, 2018, 178, 73-81. []. [PMID: 29278785].
Jaeger, P.A.; Lucin, K.M.; Britschgi, M.; Vardarajan, B.; Huang, R.P.; Kirby, E.D.; Abbey, R.; Boeve, B.F.; Boxer, A.L.; Farrer, L.A.; Finch, N.; Graff-Radford, N.R.; Head, E.; Hofree, M.; Huang, R.; Johns, H.; Karydas, A.; Knopman, D.S.; Loboda, A.; Masliah, E.; Narasimhan, R.; Petersen, R.C.; Podtelezhnikov, A.; Pradhan, S.; Rademakers, R.; Sun, C.H.; Younkin, S.G.; Miller, B.L.; Ideker, T.; Wyss-Coray, T. Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain. Mol. Neurodegener., 2016, 11, 31. []. [PMID: 27112350].
Kang, S.; Jeong, H.; Baek, J.H.; Lee, S.J.; Han, S.H.; Cho, H.J.; Kim, H.; Hong, H.S.; Kim, Y.H.; Yi, E.C.; Seo, S.W.; Na, D.L.; Hwang, D.; Mook-Jung, I. PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer’s Disease. J. Alzheimers Dis., 2016, 53(4), 1563-1576. []. [PMID: 27392853].
Sultana, R.; Baglioni, M.; Cecchetti, R.; Cai, J.; Klein, J.B.; Bastiani, P.; Ruggiero, C.; Mecocci, P.; Butterfield, D.A. Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease. Free Radic. Biol. Med., 2013, 65, 595-606. []. [PMID: 23933528].
Kim, S.; Swaminathan, S.; Inlow, M.; Risacher, S.L.; Nho, K.; Shen, L.; Foroud, T.M.; Petersen, R.C.; Aisen, P.S.; Soares, H.; Toledo, J.B.; Shaw, L.M.; Trojanowski, J.Q.; Weiner, M.W.; McDonald, B.C.; Farlow, M.R.; Ghetti, B.; Saykin, A.J. Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel. PLoS One, 2013, 8(7)e70269 []. [PMID: 23894628].

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Article Details

Year: 2019
Page: [630 - 647]
Pages: 18
DOI: 10.2174/1570159X16666180926123722
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