AccScience Publishing / AN / Volume 3 / Issue 1 / DOI: 10.36922/an.2058
Submit to AN
Cite this article
26
Download
377
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW

Reactive antibodies against brain antigens as serological biomarkers of neurodegenerative diseases

June Egiguren-Ortiz1,2 ,  Celtia Domínguez-Fernández1,2 ,  Jone Razquin2,3 ,  Laura De las Heras-García2,4 ,  Egoitz Astigarraga1 ,  Cristina Miguelez2,3* ,  Gabriel Barreda-Gómez1*
Show Less
1 Research and Development Division, IMG Pharma Biotech S.L., Zamudio, Spain
2 Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain
3 Neurodegenerative Diseases Group, BioBizkaia Health Research Institute, Barakaldo, Spain
4 University of Bordeaux, Institute of Neurodegenerative Diseases, UMR 5293, Bordeaux, France
Advanced Neurology 2024, 3(1), 2058 https://doi.org/10.36922/an.2058
Submitted: 18 October 2023 | Accepted: 9 January 2024 | Published: 13 March 2024
© 2024 by the Author (s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

The aging of the population, attributed to increased life expectancy, coincides with a rise in the prevalence of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The symptoms of these disorders, such as motor disturbances and cognitive impairment, occur only after significant neurological damage, greatly diminishing the effectiveness of treatments. Consequently, achieving early diagnosis of neurodegenerative diseases stands as a paramount global health challenge. These conditions are characterized by the progressive loss of specific neuronal groups in the nervous system, resulting in dysfunction and eventual cell death in the brain. Although the exact cause of neuronal degeneration remains largely unknown, recent studies have revealed the significant involvement of the immune system in the pathogenesis of these diseases. Notably, the identification of reactive antibodies targeting specific antigens has highlighted a close association between immune mechanisms and the neurodegenerative process. Thus, the aim of this review is to explore the mechanisms of the adaptive immune system and their impact on the pathogenesis of neurodegenerative diseases, with a particular focus on reactive antibodies and their potential as diagnostic biomarkers.

Keywords
Biomarker
Neurodegenerative diseases
Reactive antibodies
Adaptive immune
Funding
This work was supported by part of the Grant PID2 021-126434OB-I00 funded by MCIN/AEI/10.13039/501100011033 and ERDF A way of making Europe. It was also funded by the Basque Government (BIKAINTEK program: 005-B2/2021, 007-B2/2020; IT1706- 22 and PUE21-03) and the University of the Basque Country, UPV/EHU (PIFIND21/04, PIFI20/05 and COLAB20/07).
References
  1. Engelhardt B, Vajkoczy P, Weller RO. The movers and shapers in immune privilege of the CNS. Nat Immunol. 2017;18(2):123-131. doi: 10.1038/ni.3666

 

  1. Croese T, Castellani G, Schwartz M. Immune cell compartmentalization for brain surveillance and protection. Nat Immunol. 2021;22(9):1083-1092. doi: 10.1038/s41590-021-00994-2

 

  1. Fainstein N, Ben-Hur T. Brain region-dependent rejection of neural precursor cell transplants. Front Mol Neurosci. 2018;11:136. doi: 10.3389/fnmol.2018.00136

 

  1. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8(1):579- 621. doi: 10.1146/annurev.iy.08.040190.003051

 

  1. Kowal C, Athanassiou A, Chen H, Diamond B. Maternal antibodies and developing blood-brain barrier. Immunol Res. 2015;63(1-3):18-25. doi: 10.1007/s12026-015-8714-5

 

  1. Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20(2):136-144. doi: 10.1038/NN.4475

 

  1. Ousman SS, Kubes P. Immune surveillance in the central nervous system. Nat Neurosci. 2012;15(8):1096-1101. doi: 10.1038/nn.3161

 

  1. Baruch K, Schwartz M. CNS-specific T cells shape brain function via the choroid plexus. Brain Behav Immun. 2013;34:11-16. doi: 10.1016/j.bbi.2013.04.002

 

  1. Castellani G, Croese T, Peralta Ramos JM, Schwartz M. Transforming the understanding of brain immunity. Science. 2023;380(6640):eabo7649. doi: 10.1126/SCIENCE.ABO7649

 

  1. Berriat F, Lobsiger CS, Boillée S. The contribution of the peripheral immune system to neurodegeneration. Nat Neurosci. 2023;26(6):942-954. doi: 10.1038/S41593-023-01323-6

 

  1. Lueg G, Gross CC, Lohmann H, et al. Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer’s disease. Neurobiol Aging. 2015;36(1):81-89. doi: 10.1016/j.neurobiolaging.2014.08.008

 

  1. Gate D, Saligrama N, Leventhal O, et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature. 2020;577(7790):399-404. doi: 10.1038/s41586-019-1895-7

 

  1. Zhang J, Ke KF, Liu Z, Qiu YH, Peng YP. Th17 Cell-mediated neuroinflammation is involved in neurodegeneration of Aβ1-42-induced Alzheimer’s disease model rats. PLoS One. 2013;8(10):e75786. doi: 10.1371/journal.pone.0075786

 

  1. Monsonego A, Nemirovsky A, Harpaz I. CD4 T cells in immunity and immunotherapy of Alzheimer’s disease. Immunology. 2013;139(4):438-446. doi: 10.1111/imm.12103

 

  1. Bouras C, Riederer BM, Kövari E, Hof PR, Giannakopoulos P. Humoral immunity in brain aging and Alzheimer’s disease. Brain Res Brain Res Rev. 2005;48(3):477-487. doi: 10.1016/j.brainresrev.2004.09.009

 

  1. Marsh SE, Abud EM, Lakatos A, et al. The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function. Proc Natl Acad Sci U S A. 2016;113(9):E1316-E1325. doi: 10.1073/pnas.1525466113

 

  1. Lindestam Arlehamn CS, Dhanwani R, Pham J, et al. α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nat Commun. 2020;11(1):1875. doi: 10.1038/s41467-020-15626-w

 

  1. Brochard V, Combadière B, Prigent A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest. 2009;119(1):182-192. doi: 10.1172/JCI36470

 

  1. Harms AS, Ferreira SA, Romero-Ramos M. Periphery and brain, innate and adaptive immunity in Parkinson’s disease. Acta Neuropathol. 2021;141(4):527-545. doi: 10.1007/s00401-021-02268-5

 

  1. Williams-Gray CH, Wijeyekoon R, Yarnall AJ, et al. Serum immune markers and disease progression in an incident Parkinson’s disease cohort (ICICLE-PD). Mov Disord. 2016;31(7):995-1003. doi: 10.1002/mds.26563

 

  1. Mason DW, Charlton HM, Jones AJ, Lavy CB, Puklavec M, Simmonds SJ. The fate of allogeneic and xenogeneic neuronal tissue transplanted into the third ventricle of rodents. Neuroscience. 1986;19(3):685-694. doi: 10.1016/0306-4522(86)90292-7

 

  1. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172(4379):603-606. doi: 10.1038/172603A0

 

  1. Mapunda JA, Tibar H, Regragui W, Engelhardt B. How Does the immune system enter the brain? Front Immunol. 2022;13:805657. doi: 10.3389/FIMMU.2022.805657

 

  1. Dorrier CE, Jones HE, Pintarić L, Siegenthaler JA, Daneman R. Emerging roles for CNS fibroblasts in health, injury and disease. Nat Rev Neurosci. 2022;23(1):23-34. doi: 10.1038/s41583-021-00525-w

 

  1. Louveau A, Smirnov I, Keyes TJ, et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337-341. doi: 10.1038/nature14432

 

  1. Da Mesquita S, Fu Z, Kipnis J. The meningeal lymphatic system: A new player in neurophysiology. Neuron. 2018;100(2):375-388. doi: 10.1016/j.neuron.2018.09.022

 

  1. Alcolado R, Weller RO, Parrish EP, Garrod D. The cranial arachnoid and pia mater in man: Anatomical and ultrastructural observations. Neuropathol Appl Neurobiol. 1988;14(1):1-17. doi: 10.1111/J.1365-2990.1988.TB00862.X

 

  1. Hutchings M, Weller RO. Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg. 1986;65(3):316-325. doi: 10.3171/jns.1986.65.3.0316

 

  1. Decimo I, Fumagalli G, Berton V, Krampera M, Bifari F. Meninges: From protective membrane to stem cell niche. Am J Stem Cell. 2012;1(2):92-105.

 

  1. Howell OW, Schulz-Trieglaff EK, Carassiti D, et al. Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space. Neuropathol Appl Neurobiol. 2015;41(6):798-813. doi: 10.1111/nan.12199

 

  1. Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: Function and dysfunction. Semin Immunopathol. 2009;31(4):497-511. doi: 10.1007/s00281-009-0177-0

 

  1. Tietz S, Engelhardt B. Brain barriers: Crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209(4):493-506. doi: 10.1083/jcb.201412147

 

  1. Liebner S, Dijkhuizen RM, Reiss Y, Plate KH, Agalliu D, Constantin G. Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol. 2018;135(3):311-336. doi: 10.1007/s00401-018-1815-1

 

  1. Iwasaki A. Immune regulation of antibody access to neuronal tissues. Trends Mol Med. 2017;23(3):227-245. doi: 10.1016/j.molmed.2017.01.004

 

  1. Wolburg H, Paulus W. Choroid plexus: Biology and pathology. Acta Neuropathol. 2010;119(1):75-88. doi: 10.1007/s00401-009-0627-8

 

  1. Castro Dias M, Mapunda JA, Vladymyrov M, Engelhardt B. Structure and junctional complexes of endothelial, epithelial and glial brain barriers. Int J Mol Sci. 2019;20(21):5372. doi: 10.3390/ijms20215372

 

  1. Ghersi-Egea J-F, Strazielle N, Catala M, Silva-Vargas V, Doetsch F, Engelhardt B. Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 2018;135(3):337-361. doi: 10.1007/s00401-018-1807-1

 

  1. Habib N, McCabe C, Medina S, et al. Disease-associated astrocytes in Alzheimer’s disease and aging. Nat Neurosci. 2020;23(6):701-706. doi: 10.1038/s41593-020-0624-8

 

  1. Lee CYD, Daggett A, Gu X, et al. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer’s disease models. Neuron. 2018;97(5):1032-1048.e5. doi: 10.1016/j.neuron.2018.02.002

 

  1. Wang Y, Cella M, Mallinson K, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell. 2015;160(6):1061-1071. doi: 10.1016/j.cell.2015.01.049

 

  1. Jay TR, Hirsch AM, Broihier ML, et al. Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer’s disease. J Neurosci. 2017;37(3):637-647. doi: 10.1523/JNEUROSCI.2110-16.2016

 

  1. Labzin LI, Heneka MT, Latz E. Innate immunity and neurodegeneration. Annu Rev Med. 2018;69:437-449. doi: 10.1146/annurev-med-050715

 

  1. DeMaio A, Mehrotra S, Sambamurti K, Husain S. The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases. J Neuroinflammation. 2022;19(1):251. doi: 10.1186/S12974-022-02605-9

 

  1. Cunningham MW. Molecular mimicry, autoimmunity, and infection: The cross-reactive antigens of group a Streptococci and their Sequelae. Microbiol Spectr. 2019;7(4):10-1128. doi: 10.1128/microbiolspec.gpp3-0045-2018

 

  1. Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: A comprehensive update. J Intern Med. 2015;278(4):369-395. doi: 10.1111/JOIM.12395

 

  1. Levin EC, Acharya NK, Han M, et al. Brain-reactive autoantibodies are nearly ubiquitous in human sera and may be linked to pathology in the context of blood-brain barrier breakdown. Brain Res. 2010;1345:221-232. doi: 10.1016/j.brainres.2010.05.038

 

  1. Webb NE, Bernshtein B, Alter G. Tissues: The unexplored frontier of antibody mediated immunity. Curr Opin Virol. 2021;47:52-67. doi: 10.1016/j.coviro.2021.01.001

 

  1. Nagaraj V, Theis T, Johal AS, et al. Application of antibodies to neuronally expressed nogo-a increases neuronal survival and neurite outgrowth. Int J Mol Sci. 2020;21(15):5417. doi: 10.3390/ijms21155417

 

  1. Ineichen BV, Kapitza S, Bleul C, et al. Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta Neuropathol. 2017;134(3):423-440. doi: 10.1007/s00401-017-1745-3

 

  1. Ma H, Murphy C, Loscher CE, O’Kennedy R. RAutoantibodies-enemies, and/or potential allies? Front Immunol. 2022;13:953726. doi: 10.3389/fimmu.2022.953726

 

  1. Cocco C, Manca E, Corda G, et al. Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus. Front Immunol. 2023;14:1157149. doi: 10.3389/fimmu.2023.1157149

 

  1. Mader S, Brimberg L, Diamond B. The role of brain-reactive autoantibodies in brain pathology and cognitive impairment. Front Immunol. 2017;8:1101. doi: 10.3389/fimmu.2017.01101

 

  1. Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2019;16(9):535-548. doi: 10.1038/s41571-019-0194-4

 

  1. Daguano Gastaldi V, BH Wilke J, Weidinger CA, et al. Factors predisposing to humoral autoimmunity against brain-antigens in health and disease: Analysis of 49 autoantibodies in over 7000 subjects. Brain Behav Immun. 2023;108:135-147. doi: 10.1016/J.BBI.2022.10.016

 

  1. Hohlfeld R, Dornmair K, Meinl E, Wekerle H. The search for the target antigens of multiple sclerosis, part 2: CD8+ T cells, B cells, and antibodies in the focus of reverse-translational research. Lancet Neurol. 2016;15(3):317-331. doi: 10.1016/S1474-4422(15)00313-0

 

  1. Van Coevorden-Hameete MH, Titulaer MJ, Schreurs MWJ, de Graaff E, Sillevis Smitt PAE, Hoogenraad CC. Detection and characterization of autoantibodies to neuronal cell-surface antigens in the central nervous system. Front Mol Neurosci. 2016;9:197972. doi: 10.3389/FNMOL.2016.00037/BIBTEX

 

  1. Yin J, Ibrahim S, Petersen F, Yu X. Autoimmunomic signatures of aging and age-related neurodegenerative diseases are associated with brain function and ribosomal proteins. Front Aging Neurosci. 2021;13:679688. doi: 10.3389/FNAGI.2021.679688

 

  1. Hansen N, Malchow B, Zerr I, Stöcker W, Wiltfang J, Timäus C. Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort. J Neural Transm (Vienna). 2021;128(3):357. doi: 10.1007/S00702-021-02316-0

 

  1. Arshad F, Varghese F, Paplikar A, et al. Role of Autoantibodies in Neurodegenerative Dementia: An Emerging Association. Dement Geriatr Cogn Disord. 2021;50(2):153-160. doi: 10.1159/000517238

 

  1. Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019;14:5541-5554. doi: 10.2147/IJN.S200490

 

  1. Chandupatla RR, Flatley A, Feederle R, Mandelkow EM, Kaniyappan S. Novel antibody against low-n oligomers of tau protein promotes clearance of tau in cells via lysosomes. Alzheimers Dement (N Y). 2020;6(1):e12097. doi: 10.1002/trc2.12097

 

  1. Zilkova M, Nolle A, Kovacech B, et al. Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation. Acta Neuropathol Commun. 2020;8(1):74. doi: 10.1186/s40478-020-00948-z

 

  1. Congdon EE, Pan R, Jiang Y, et al. Single domain antibodies targeting pathological tau protein: Influence of four IgG subclasses on efficacy and toxicity. EBioMedicine. 2022;84:104249. doi: 10.1016/j.ebiom.2022.104249

 

  1. Lee SH, Le Pichon CE, Adolfsson O, et al. Antibody-mediated targeting of tau in vivo does not require effector function and microglial engagement. Cell Rep. 2016;16(6):1690-1700. doi: 10.1016/j.celrep.2016.06.099

 

  1. Nagele RG, Clifford PM, Siu G, et al. Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β(1-42) deposition. J Alzheimers Dis. 2011;25(4):605-622. doi: 10.3233/JAD-2011-110098

 

  1. Vojdani A, Vojdani E. Amyloid-beta 1-42 cross-reactive antibody prevalent in human sera may contribute to intraneuronal deposition of A-Beta-P-42. Int J Alzheimers Dis. 2018;2018:1672568. doi: 10.1155/2018/1672568

 

  1. Deng J, Hou H, Giunta B, et al. Autoreactive-Aβ antibodies promote APP β-secretase processing. J Neurochem. 2012;120(5):732-740. doi: 10.1111/j.1471-4159.2011.07629.x

 

  1. Gold M, Mengel D, Röskam S, Dodel R, Bach JP. Mechanisms of action of naturally occurring antibodies against β-amyloid on microglia. J Neuroinflammation. 2013;10(1):5. doi: 10.1186/1742-2094-10-5

 

  1. Valls-Comamala V, Guivernau B, Bonet J, et al. The antigen-binding fragment of human gamma immunoglobulin prevents amyloid β-peptide folding into β-sheet to form oligomers. Oncotarget. 2017;8(25):41154-41165. doi: 10.18632/oncotarget.17074

 

  1. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3(1):17013. doi: 10.1038/nrdp.2017.13

 

  1. Bae EJ, Lee HJ, Rockenstein E, et al. Antibody-aided clearance of extracellular α-synuclein prevents cell-to-cell aggregate transmission. J Neurosci. 2012;32(39):13454-13469. doi: 10.1523/JNEUROSCI.1292-12.2012

 

  1. Nordström E, Eriksson F, Sigvardson J, et al. ABBV-0805, a novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson’s disease. Neurobiol Dis. 2021;161:105543. doi: 10.1016/j.nbd.2021.105543

 

  1. Li X, Koudstaal W, Fletcher L, et al. Naturally occurring antibodies isolated from PD patients inhibit synuclein seeding in vitro and recognize Lewy pathology. Acta Neuropathol. 2019;137(5):825-836. doi: 10.1007/s00401-019-01974-5

 

  1. Cascella R, Perni M, Chen SW, et al. Probing the origin of the toxicity of oligomeric aggregates of α-synuclein with antibodies. ACS Chem Biol. 2019;14(6):1352-1362. doi: 10.1021/acschembio.9b00312

 

  1. Näsström T, Gonçalves S, Sahlin C, et al. Antibodies against alpha-synuclein reduce oligomerization in living cells. PLoS One. 2011;6(10):e27230. doi: 10.1371/journal.pone.0027230

 

  1. Orr CF, Rowe DB, Mizuno Y, Mori H, Halliday GM. A possible role for humoral immunity in the pathogenesis of Parkinson’s disease. Brain. 2005;128(11):2665-2674. doi: 10.1093/brain/awh625

 

  1. Wang XJ, Yan ZQ, Lu GQ, Stuart S, Chen SD. Parkinson disease IgG and C5a-induced synergistic dopaminergic neurotoxicity: Role of microglia. Neurochem Int. 2007;50(1):39-50. doi: 10.1016/j.neuint.2006.07.014

 

  1. Cao S, Theodore S, Standaert DG. Fcγ receptors are required for NF-κB signaling, microglial activation and dopaminergic neurodegeneration in an AAV-synuclein mouse model of Parkinson’s disease. Mol Neurodegener. 2010;5(1):42. doi: 10.1186/1750-1326-5-42

 

  1. Choi YR, Cha SH, Kang SJ, Kim JB, Jou I, Park SM. Prion-like propagation of α-synuclein is regulated by the FcγRIIB-SHP-1/2 signaling pathway in neurons. Cell Rep. 2018;22(1):136-148. doi: 10.1016/j.celrep.2017.12.009

 

  1. Tabrizi SJ, Flower MD, Ross CA, Wild EJ. Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol. 2020;16(10):529-546. doi: 10.1038/s41582-020-0389-4

 

  1. Bayram-Weston Z, Jones L, Dunnett SB, Brooks SP, et al. Comparison of mHTT antibodies in Huntington’s disease mouse models reveal specific binding profiles and steady-state ubiquitin levels with disease development. PLoS One. 2016;11(5):e0155834. doi: 10.1371/journal.pone.0155834

 

  1. Lee DH, Heidecke H, Schröder A, et al. Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease. Mol Neurodegener. 2014;9(1):49. doi: 10.1186/1750-1326-9-49

 

  1. Endres D, Werden R, Schweizer T, et al. Novel neuronal autoantibodies in Huntington’s disease. Biol Psychiatry. 2022;91(4):e21-e23. doi: 10.1016/j.biopsych.2020.12.032

 

  1. Masrori P, Van Damme P. Amyotrophic lateral sclerosis: A clinical review. Eur J Neurol. 2020;27(10):1918-1929. doi: 10.1111/ene.14393

 

  1. Tafuri F, Ronchi D, Magri F, Comi GP, Corti S. SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis. Front Cell Neurosci. 2015;9:336. doi: 10.3389/FNCEL.2015.00336

 

  1. Conti E, Sala G, Diamanti S, et al. Serum naturally occurring anti-TDP-43 auto-antibodies are increased in amyotrophic lateral sclerosis. Sci Rep. 2021;11(1):1978. doi: 10.1038/s41598-021-81599-5

 

  1. Nielsen AK, Folke J, Owczarek S, et al. TDP-43-specific autoantibody decline in patients with amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021;8(2):e937. doi: 10.1212/NXI.0000000000000937

 

  1. Riemenschneider H, Simonetti F, Sheth U, et al. Targeting the glycine-rich domain of TDP-43 with antibodies prevents its aggregation in vitro and reduces neurofilament levels in vivo. Acta Neuropathol Commun. 2023;11(1):112. doi: 10.1186/s40478-023-01592-z

 

  1. Atlasi RS, Malik R, Corrales CI, et al. Investigation of anti- SOD1 antibodies yields new structural insight into SOD1 misfolding and surprising behavior of the antibodies themselves. ACS Chem Biol. 2018;13(9):2794-2807. doi: 10.1021/acschembio.8b00729

 

  1. Niebroj-Dobosz I, Dziewulska D, Janik P. Auto-antibodies against proteins of spinal cord cells in cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Folia Neuropathol. 2006;44(3):191-196.

 

  1. Sugimoto K, Mori M, Liu J, et al. Novel serum autoantibodies against ß-actin (ACTB) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2021;22(5- 6):388-394. doi: 10.1080/21678421.2021.1885448

 

  1. Domínguez-Fernández C, Egiguren-Ortiz J, Razquin J, et al. Review of technological challenges in personalised medicine and early diagnosis of neurodegenerative disorders. Int J Mol Sci. 2023;24(4):3321. doi: 10.3390/ijms24043321

 

  1. Gaetani L, Paolini Paoletti F, Bellomo G, et al. CSF and blood biomarkers in neuroinflammatory and neurodegenerative diseases: Implications for treatment. Trends Pharmacol Sci. 2020;41(12):1023-1037. doi: 10.1016/j.tips.2020.09.011

 

  1. Diamond B, Honig G, Mader S, Brimberg L, Volpe BT. Brain-reactive antibodies and disease. Annu Rev Immunol. 2013;31(1):345-385. doi: 10.1146/annurev-immunol-020711-075041

 

  1. Baril L, Nicolas L, Croisile B, et al. Immune response to Abeta-peptides in peripheral blood from patients with Alzheimer’s disease and control subjects. Neurosci Lett. 2004;355(3):226-230. doi: 10.1016/j.neulet.2003.10.071

 

  1. Weksler ME, Relkin N, Turkenich R, LaRusse S, Zhou L, Szabo P. Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp Gerontol. 2002;37(7):943-948. doi: 10.1016/S0531-5565(02)00029-3

 

  1. Qu BX, Gong Y, Moore C, et al. Beta-amyloid auto-antibodies are reduced in Alzheimer’s disease. J Neuroimmunol. 2014;274(1-2):168-173. doi: 10.1016/j.jneuroim.2014.06.017

 

  1. Brettschneider S, Morgenthaler NG, Teipel SJ, et al. Decreased serum amyloid beta(1-42) autoantibody levels in Alzheimer’s disease, determined by a newly developed immuno-precipitation assay with radiolabeled amyloid beta(1-42) peptide. Biol Psychiatry. 2005;57(7):813-816. doi: 10.1016/j.biopsych.2004.12.008

 

  1. Song M, Mook-Jung I, Lee H, Min JY, Park MH. Serum anti-amyloid-beta antibodies and Alzheimer’s disease in elderly Korean patients. J Int Med Res. 2007;35(3):301-306. doi: 10.1177/147323000703500303

 

  1. Nath A, Hall E, Tuzova M, et al. Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer’s disease patients and Abeta antibodies can enhance Abeta neurotoxicity: Implications for disease pathogenesis and vaccine development. Neuromolecular Med. 2003;3(1):29-30. doi: 10.1385/NMM:3:1:29

 

  1. Maftei M, Thurm F, Schnack C, et al. Increased levels of antigen-bound β-amyloid autoantibodies in serum and cerebrospinal fluid of Alzheimer’s disease patients. PLoS One. 2013;8(7):e68996. doi: 10.1371/journal.pone.0068996

 

  1. Gustaw-Rothenberg KA, Siedlak SL, Bonda DJ, et al. Dissociated amyloid-β antibody levels as a serum biomarker for the progression of Alzheimer’s disease: A population-based study. Exp Gerontol. 2010;45(1):47-52. doi: 10.1016/j.exger.2009.10.003

 

  1. Bartos A, Fialová L, Švarcová J. Lower serum antibodies against tau protein and heavy neurofilament in Alzheimer’s disease. J Alzheimers Dis. 2018;64(3):751-760. doi: 10.3233/JAD-180039

 

  1. Krestova M, Ricny J, Bartos A. Changes in concentrations of tau-reactive antibodies are dependent on sex in Alzheimer’s disease patients. J Neuroimmunol. 2018;322:1-8. doi: 10.1016/j.jneuroim.2018.05.004

 

  1. Klaver AC, Coffey MP, Bennett DA, Loeffler DA. Specific serum antibody binding to phosphorylated and non-phosphorylated tau in non-cognitively impaired, mildly cognitively impaired, and Alzheimer’s disease subjects: An exploratory study. Transl Neurodegener. 2017;6(1):32. doi: 10.1186/s40035-017-0100-x

 

  1. Yanamandra K, Gruden MA, Casaite V, Meskys R, Forsgren L, Morozova-Roche LA. α-Synuclein reactive antibodies as diagnostic biomarkers in blood sera of Parkinson’s disease patients. PLoS One. 2011;6(4):e18513. doi: 10.1371/journal.pone.0018513

 

  1. Shalash A, Salama M, Makar M, et al. Elevated serum α-synuclein autoantibodies in patients with parkinson’s disease relative to Alzheimer’s disease and controls. Front Neurol. 2017;8:720. doi: 10.3389/fneur.2017.00720

 

  1. Xu Q, Evetts S, Hu M, Talbot K, Wade-Martins R, Davis JJ. An impedimetric assay of α-synuclein autoantibodies in early stage Parkinson’s disease. RSC Adv. 2014;4(102):58773-58777. doi: 10.1039/c4ra10100f

 

  1. Bryan T, Luo X, Forsgren L, Morozova-Roched LA, Davis JJ. The robust electrochemical detection of a Parkinson’s disease marker in whole blood sera. Chem Sci. 2012;3(12):3468-3473. doi: 10.1039/c2sc21221h

 

  1. Gruden MA, Sewell RDE, Yanamandra K, et al. Immunoprotection against toxic biomarkers is retained during Parkinson’s disease progression. J Neuroimmunol. 2011;233(1-2):221-227. doi: 10.1016/j.jneuroim.2010.12.001

 

  1. Akhtar RS, Licata JP, Luk KC, Shaw LM, Trojanowski JQ, Lee VM. Measurements of auto-antibodies to α-synuclein in the serum and cerebral spinal fluids of patients with Parkinson’s disease. J Neurochem. 2018;145(6):489-503. doi: 10.1111/jnc.14330

 

  1. Maetzler W, Apel A, Langkamp M, et al. Comparable autoantibody serum levels against amyloid- and inflammation-associated proteins in Parkinson’s disease patients and controls. PLoS One. 2014;9(2):e88604. doi: 10.1371/journal.pone.0088604

 

  1. Smith LM, Schiess MC, Coffey MP, Klaver AC, Loeffler DA. α-Synuclein and anti-α-synuclein antibodies in Parkinson’s disease, atypical Parkinson syndromes, REM sleep behavior disorder, and healthy controls. PLoS One. 2012;7(12):e52285. doi: 10.1371/journal.pone.0052285

 

  1. Besong-Agbo D, Wolf E, Jessen F, et al. Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease. Neurology. 2013;80(2):169-175. doi: 10.1212/WNL.0b013e31827b90d1

 

  1. Tzartos JS, Zisimopoulou P, Rentzos M, et al. LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients. Ann Clin Transl Neurol. 2014;1(2):80-87. doi: 10.1002/acn3.26

 

  1. Fialová L, Švarcová J, Bartos A, et al. Cerebrospinal fluid and serum antibodies against neurofilaments in patients with amyotrophic lateral sclerosis. Eur J Neurol. 2010;17(4):562-566. doi: 10.1111/j.1468-1331.2009.02853.x

 

  1. Messer A, Butler DC. Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders. Neurobiol Dis. 2020;134:104619. doi: 10.1016/J.NBD.2019.104619

 

  1. Asefy Z, Hoseinnejhad S, Ceferov Z. Nanoparticles approaches in neurodegenerative diseases diagnosis and treatment. Neurol Sci. 2021;42(7):2653-2660. doi: 10.1007/S10072-021-05234-X

 

  1. Van Dyck CH. Anti-amyloid-β monoclonal antibodies for Alzheimer’s disease: Pitfalls and promise. Biol Psychiatry. 2018;83(4):311-319. doi: 10.1016/j.biopsych.2017.08.010

 

  1. Arndt JW, Qian F, Smith BA, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Sci Rep. 2018;8(1):6412. doi: 10.1038/s41598-018-24501-0

 

  1. Lu M, Brashear HR. Pharmacokinetics, pharmacodynamics, and safety of subcutaneous bapineuzumab: A single-ascending-dose study in patients with mild to moderate Alzheimer disease. Clin Pharmacol Drug Dev. 2019;8(3):326-335. doi: 10.1002/cpdd.584

 

  1. Black RS, Sperling RA, Safirstein B, et al. A single ascending dose study of bapineuzumab in patients with alzheimer disease. Alzheimer Dis Assoc Disord. 2010;24(2):198-203. doi: 10.1097/WAD.0b013e3181c53b00

 

  1. Salloway SP, Sperling R, Fox NC, et al. Long-term follow up of patients with mild-to-moderate Alzheimer’s disease treated with bapineuzumab in a Phase III, open-label, extension study. J Alzheimers Dis. 2018;64(3):689-707. doi: 10.3233/JAD-171157

 

  1. Novak G, Fox N, Clegg S, et al. Changes in brain volume with bapineuzumab in mild to moderate Alzheimer’s disease. J Alzheimers Dis. 2015;49(4):1123-1134. doi: 10.3233/JAD-150448

 

  1. Salloway S, Sperling R, Fox NC, et al. Two Phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):322-333. doi: 10.1056/nejmoa1304839

 

  1. Vandenberghe R, Rinne JO, Boada M, et al. Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials. Alzheimers Res Ther. 2016;8(1):18. doi: 10.1186/s13195-016-0189-7

 

  1. Abushouk AI, Elmaraezy A, Aglan A, et al. Bapineuzumab for mild to moderate Alzheimer’s disease: A meta-analysis of randomized controlled trials. BMC Neurol. 2017;17(1):66. doi: 10.1186/s12883-017-0850-1

 

  1. Farlow M, Arnold SE, Van Dyck CH, et al. Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement. 2012;8(4):261- 271. doi: 10.1016/j.jalz.2011.09.224

 

  1. Siemers ER, Friedrich S, Dean RA, et al. Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol. 2010;33(2):67-73. doi: 10.1097/WNF.0b013e3181cb577a

 

  1. Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370(4):311-321. doi: 10.1056/nejmoa1312889

 

  1. Willis BA, Sundell K, Lachno DR, et al. Central pharmacodynamic activity of solanezumab in mild Alzheimer’s disease dementia. Alzheimers Dement (N Y). 2018;4:652-660. doi: 10.1016/j.trci.2018.10.001

 

  1. Liu-Seifert H, Siemers E, Holdridge KC, et al. Delayed-start analysis: Mild Alzheimer’s disease patients in solanezumab trials, 3.5 years. Alzheimers Dement (N Y). 2015;1(2):111-121. doi: 10.1016/j.trci.2015.06.006

 

  1. Samadi H, Sultzer D. Solanezumab for Alzheimer’s disease. Expert Opin Biol Ther. 2011;11(6):787-798. doi: 10.1517/14712598.2011.578573

 

  1. Nisticò R, Novakovic D, Feligioni M, et al. Profile of gantenerumab and its potential in the treatment of Alzheimer’s disease. Drug Des Devel Ther. 2013;7:1359-1364. doi: 10.2147/DDDT.S53401

 

  1. Klein G, Delmar P, Voyle N, et al. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: A PET substudy interim analysis. Alzheimers Res Ther. 2019;11(1):101. doi: 10.1186/s13195-019-0559-z

 

  1. Ostrowitzki S, Lasser RA, Dorflinger E, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res Ther. 2017;9(1):95. doi: 10.1186/s13195-017-0318-y

 

  1. Bateman RJ, Cummings J, Schobel S, et al. Gantenerumab: An anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease. Alzheimers Res Ther. 2022;14(1):178. doi: 10.1186/s13195-022-01110-8

 

  1. Panza F, Solfrizzi V, Imbimbo BP, et al. Efficacy and safety studies of gantenerumab in patients with Alzheimer’s disease. Expert Rev Neurother. 2014;14(9):973-986. doi: 10.1586/14737175.2014.945522

 

  1. Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69(2):198-207. doi: 10.1001/archneurol.2011.1538

 

  1. Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: A novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. J Alzheimers Dis. 2012;28(1):49-69. doi: 10.3233/JAD-2011-110977

 

  1. Retout S, Gieschke R, Serafin D, Weber C, Frey N, Hofmann C. Disease modeling and model-based meta-analyses to define a new direction for a phase III program of gantenerumab in Alzheimer’s disease. Clin Pharmacol Ther. 2022;111(4):857-866. doi: 10.1002/cpt.2535

 

  1. Yang P, Sun F. Aducanumab: The first targeted Alzheimer’s therapy. Drug Discov Ther. 2021;15(3):166-168. doi: 10.5582/ddt.2021.01061

 

  1. Budd Haeberlein S, Aisen PS, Barkhof F, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimers Dis. 2022;9(2):197-210. doi: 10.14283/jpad.2022.30

 

  1. Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537(7618):50-56. doi: 10.1038/nature19323

 

  1. Ferrero J, Williams L, Stella H, et al. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement (N Y). 2016;2(3):169-176. doi: 10.1016/j.trci.2016.06.002

 

  1. Vaz M, Silva V, Monteiro C, Silvestre S. Role of aducanumab in the treatment of Alzheimer’s disease: Challenges and opportunities. Clin Interv Aging. 2022;17:797-810. doi: 10.2147/CIA.S325026

 

  1. Salloway S, Chalkias S, Barkhof F, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022;79(1):13-21. doi: 10.1001/jamaneurol.2021.4161

 

  1. Day GS, Scarmeas N, Dubinsky R, et al. Aducanumab use in symptomatic alzheimer disease evidence in focus. Neurology. 2022;98(15):619-631. doi: 10.1212/WNL.0000000000200176

 

  1. Tucker S, Möller C, Tegerstedt K, et al. The murine Version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe Mice. J Alzheimers Dis. 2015;43(2):575-588. doi: 10.3233/JAD-140741

 

  1. Dhadda S, Kanekiyo M, Li D, et al. Consistency of efficacy results across various clinical measures and statistical methods in the lecanemab phase 2 trial of early Alzheimer’s disease. Alzheimers Res Ther. 2022;14(1):182. doi: 10.1186/s13195-022-01129-x

 

  1. Tahami Monfared AA, Tafazzoli A, Chavan A, et al. The potential economic value of lecanemab in patients with early Alzheimer’s disease using simulation modeling. Neurol Ther. 2022;11(3):1285-1307. doi: 10.1007/s40120-022-00373-5

 

  1. Tahami Monfared AA, Tafazzoli A, Ye W, Chavan A, Zhang Q. Long-term health outcomes of lecanemab in patients with early Alzheimer’s disease using simulation modeling. Neurol Ther. 2022;11(2):863-880. doi: 10.1007/s40120-022-00350-y

 

  1. Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80. doi: 10.1186/s13195-021-00813-8

 

  1. McDade E, Cummings JL, Dhadda S, et al. Lecanemab in patients with early Alzheimer’s disease: Detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022;14(1):191. doi: 10.1186/s13195-022-01124-2

 

  1. Adolfsson O, Pihlgren M, Toni N, et al. An effector-reduced anti-β-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci. 2012;32(28):9677-9689. doi: 10.1523/JNEUROSCI.4742-11.2012

 

  1. Ultsch M, Li B, Maurer T, et al. Structure of crenezumab complex with aβ shows loss of β-hairpin. Sci Rep. 2016;6(1):39374. doi: 10.1038/srep39374

 

  1. Yang T, Dang Y, Ostaszewski B, et al. Target engagement in an Alzheimer trial: Crenezumab lowers amyloid β oligomers in cerebrospinal fluid. Ann Neurol. 2019;86(2):215-224. doi: 10.1002/ana.25513

 

  1. Cummings JL, Cohen S, van Dyck CH, et al. ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Neurology. 2018;90(21):e1889-e1897. doi: 10.1212/wnl.0000000000005550

 

  1. Tariot PN, Lopera F, Langbaum JB, et al. The Alzheimer’s Prevention Initiative Autosomal-Dominant Alzheimer’s Disease Trial: A study of crenezumab versus placebo in preclinical PSEN1 E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal-dominant Alzheimer’s disease, including a placebo-treated noncarrier cohort. Alzheimers Dement (N Y). 2018;4:150-160. doi: 10.1016/j.trci.2018.02.002

 

  1. Armour KL, Van De Winkel JGJ, Williamson LM, ClarkM. Differential binding to human FcgammaRIIa and FcgammaRIIb receptors by human IgG wildtype and mutant antibodies. Mol Immunol. 2003;40(9):585-593. doi: 10.1016/j.molimm.2003.08.004

 

  1. Landen JW, Andreasen N, Cronenberger CL, et al., Ponezumab in mild-to-moderate Alzheimer’s disease: Randomized phase II PET-PIB study. Alzheimers Dement (N Y). 2017;3(3):393-401. doi: 10.1016/j.trci.2017.05.003

 

  1. Landen JW, Cohen S, Billing CB Jr, et al. Multiple-dose ponezumab for mild-to-moderate Alzheimer’s disease: Safety and efficacy. Alzheimers Dement (N Y). 2017;3(3):339-347. doi: 10.1016/j.trci.2017.04.003

 

  1. Burstein AH, Zhao Q, Ross J, et al. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate alzheimer disease. Clin Neuropharmacol. 2013;36(1):8-13. doi: 10.1097/WNF.0b013e318279bcfa

 

  1. Gustafsson G, Eriksson F, Möller C, et al. Cellular uptake of α-Synuclein oligomer-selective antibodies is enhanced by the extracellular presence of α-synuclein and mediated via Fcγ receptors. Cell Mol Neurobiol. 2017;37(1):121-131. doi: 10.1007/S10571-016-0352-5

 

  1. Lindström V, Fagerqvist T, Nordström E, et al. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice. Neurobiol Dis. 2014;69:13-143. doi: 10.1016/J.NBD.2014.05.009

 

  1. Shahaduzzaman M, Nash K, Hudson C, et al. Anti-human α-synuclein N-terminal peptide antibody protects against dopaminergic cell death and ameliorates behavioral deficits in an AAV-α-synuclein rat model of Parkinson’s disease. PLoS One. 2015;10(2):e0116841. doi: 10.1371/JOURNAL.PONE.0116841

 

  1. Jankovic J, Goodman I, Safirstein B, et al. Safety and Tolerability of Multiple Ascending Doses of PRX002/ RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients with Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2018;75(10):1206-1214. doi: 10.1001/jamaneurol.2018.1487

 

  1. Masliah E, Rockenstein E, Mante M, et al. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of lewy body disease. PLoS One. 2011;6(4):e19338. doi: 10.1371/journal.pone.0019338

 

  1. Schenk DB, Koller M, Ness DK, et al. First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211-218. doi: 10.1002/mds.26878

 

  1. Weihofen A, Liu YT, Arndt JW, et al. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol Dis. 2019;124:276-288. doi: 10.1016/j.nbd.2018.10.016

 

  1. Brys M, Fanning L, Hung S, et al. Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054. Mov Disord. 2019;34(8):1154-1163. doi: 10.1002/mds.27738
Conflict of interest
The authors declare no conflicts of interest.
Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept