Skip to main content Skip to main navigation menu Skip to site footer
  • \
    Start Submission Become a Reviewer

    Characterization of a new set of monoclonal β-amyloid antibodies

    • Huan-Yu Che
    • Jia-Qi Ai
    • Chen Yang
    • Xiao-Lu Cai
    • Yan Wang
    • Juan Jiang
    • Qi-Lei Zhang
    • Tian Tu
    • Ewen Tu
    • Chong Che
    • Xiao-Xin Yan


    Abstract

    β-Amyloid (Aβ) deposition is a commonly studied neuropathology in the human brain, occurring as compact and diffuse parenchymal plaques, cerebral amyloid angiopathy (CAA), and meningeal/subpial amyloidosis. Compact plaques associated with dystrophic neurites generally referred to as neuritic plaques, are a pathological hallmark of Alzheimer's disease (AD). We evaluated three recently developed monoclonal mouse antibodies against Aβ (A1, A2 and A3) using appropriate tissue samples and assay controls in the present study. In immunohistochemistry, antibodies A1, A2 and A3 displayed all forms of cerebral Aβ deposition in a range of dilutions in cryostat and paraffin sections. These labeled profiles appeared morphologically comparable to that visualized by two commercial Aβ antibody clones, 6E10 and D12B2. In immune-dot blotting assays, antibodies A1, A2 and A3 at highly diluted concentrations detected an increase of Aβ in neocortical lysates of AD samples compared to control. Moreover, these antibodies clearly labeled Aβ pathology in brain sections of three commonly used transgenic mouse models of AD, namely, APP/PS1 mice, 5XFAD mice, and 3XTg-AD mice. Taken together, these monoclonal mouse anti-Aβ antibodies can serve as new experimental tools for basic, translational, and diagnostic research into aging and AD-related cerebral Aβ neuropathology in both human and experimental animal brains.   

    Keywords: Brain aging Dementia Neurodegeneration Neuritic plaque Proteostasis Vps10p
    Section

    References

    1. Alawode DOT, Heslegrave AJ, Ashton NJ, Karikari TK, Simrén J, Montoliu-Gaya L, Pannee J, O Connor A, Weston PSJ, Lantero-Rodriguez J, Keshavan A, Snellman A, Gobom J, Paterson RW, Schott JM, Blennow K, Fox NC, Zetterberg H. Transitioning from cerebrospinal fluid to blood tests to facilitate diagnosis and disease monitoring in Alzheimer's disease. J Intern Med. 2021; 290(3):583-601.
    2. Alonso Adel C, ElAkkad E, Gong C, Liu F, Tanaka T, Kudo T, Tatebayashi Y, Pei J, Wang J, Khatoon S, Flory M, Ghetti B, Gozes I, Novak M, Novak M, Robakis NK, de Leon M, Iqbal M. Inge Grundke-Iqbal, Ph.D. (1937–2012): the discoverer of the abnormal hyperphosphorylation of tau in Alzheimer's disease. J Mol Neurosci. 2013; 49(2):430-5.
    3. Beach TG. A History of Senile Plaques: From Alzheimer to Amyloid Imaging. J Neuropathol Exp Neurol. 2022; 81(6):387-413.
    4. Braak H, Braak E. Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol. 1991; 1(3):213-6.
    5. Braak H, Del Tredici K. Are cases with tau pathology occurring in the absence of Aβ deposits part of the AD-related pathological process? Acta Neuropathol. 2014; 128(6):767-72.
    6. Cai Y, Xiong K, Zhang XM, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Chu Y, Kordower JH, Yan XX. β-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and β-amyloid accumulation. Eur J Neurosci. 2010; 32(7):1223-38.
    7. Cai Y, Zhang XM, Macklin LN, Cai H, Luo XG, Oddo S, Laferla FM, Struble RG, Rose GM, Patrylo PR, Yan XX. BACE1 elevation is involved in amyloid plaque development in the triple transgenic model of Alzheimer's disease: differential Aβ antibody labeling of early-onset axon terminal pathology. Neurotox Res. 2012; 21(2):160-74.
    8. Caselli RJ, Beach TG, Knopman DS, Graff-Radford NR. Alzheimer Disease: Scientific Breakthroughs and Translational Challenges. Mayo Clin Proc. 2017; 92(6):978-994.
    9. Checler F, Afram E, Pardossi-Piquard R, Lauritzen I. Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99? J Biol Chem. 2021; 296:100489.
    10. Cho Y, Bae HG, Okun E, Arumugam TV, Jo DG. Physiology and pharmacology of amyloid precursor protein. Pharmacol Ther. 2022; 235:108122.
    11. Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, Kholodenko D, Motter R, Sherrington R, Perry B, Yao H, Strome R, Lieberburg I, Rommens J, Kim S, Schenk D, Fraser P, St George Hyslop P, Selkoe DJ. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med. 1997; 3(1):67-72.
    12. Cong C, Zhang W, Qian X, Qiu W, Ma C. Significant Overlap of α-Synuclein, Amyloid-β, and Phospho-Tau Pathologies in Neuropathological Diagnosis of Lewy-related Pathology: Evidence from China Human Brain Bank. J Alzheimers Dis. 2021; 80(1):447-458.
    13. Critchley M. Critical Review: THE NATURE AND SIGNIFICANCE OF SENILE PLAQUES. J Neurol Psychopathol. 1929; 10(38):124-39.
    14. Cui L, Hou NN, Wu HM, Zuo X, Lian YZ, Zhang CN, Wang ZF, Zhang X, Zhu JH. Prevalence of Alzheimer's Disease and Parkinson's Disease in China: An Updated Systematical Analysis. Front Aging Neurosci. 2020;12:603854
    15. Gao Y, Liu J, Wang J, Liu Y, Zeng LH, Ge W, Ma C. Proteomic analysis of human hippocampal subfields provides new insights into the pathogenesis of Alzheimer's disease and the role of glial cells. Brain Pathol. 2022; 32(4):e13047.
    16. García-Marín V, García-López P, Freire M. Cajal’s contributions to the study of Alzheimer’s disease. J Alzheimers Dis. 2007; 12(2):161-74.
    17. Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984; 120(3):885-90.
    18. Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci U S A. 1988; 85(11):4051-5.
    19. Griffith CM, Xie MX, Qiu WY, Sharp AA, Ma C, Pan A, Yan XX, Patrylo PR. Aberrant expression of the pore-forming KATP channel subunit Kir6. 2 in hippocampal reactive astrocytes in the 3×Tg-AD mouse model and human Alzheimer's disease. Neuroscience 2016; 336: 81-101.
    20. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986; 83(13):4913-7.
    21. Guzman-Martinez L, Calfío C, Farias GA, Vilches C, Prieto R, Maccioni RB. New Frontiers in the Prevention, Diagnosis, and Treatment of Alzheimer's Disease. J Alzheimers Dis. 2021; 82(s1):S51-S63.
    22. Guzman-Martinez L, Maccioni RB, Farías GA, Fuentes P, Navarrete LP. Biomarkers for Alzheimer's Disease. Curr Alzheimer Res. 2019; 16(6):518-528.
    23. Hampel H, Vassar R, De Strooper B, Hardy J, Willem M, Singh N, Zhou J, Yan R, Vanmechelen E, De Vos A, Nisticò R, Corbo M, Imbimbo BP, Streffer J, Voytyuk I, Timmers M, Tahami Monfared AA, Irizarry M, Albala B, Koyama A, Watanabe N, Kimura T, Yarenis L, Lista S, Kramer L, Vergallo A. The β-Secretase BACE1 in Alzheimer's Disease. Biol Psychiatry. 2021; 89(8):745-756.
    24. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996; 274(5284):99-102.
    25. Hu X, Hu ZL, Li Z, Ruan CS, Qiu WY, Pan A, Li CQ, Cai Y, Shen L, Chu Y, Tang BS, Cai H, Zhou XF, Ma C, Yan XX. Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum. Front Neuroanat. 2017; 11:45.
    26. Hur JY. γ-Secretase in Alzheimer's disease. Exp Mol Med. 2022; 54(4):433-446.
    27. Jeremic D, Jiménez-Díaz L, Navarro-López JD. Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer's disease: a systematic review. Ageing Res Rev. 2021; 72:101496.
    28. Jia Y, Wang X, Chen Y, Qiu W, Ge W, Ma C. Proteomic and Transcriptomic Analyses Reveal Pathological Changes in the Entorhinal Cortex Region that Correlate Well with Dysregulation of Ion Transport in Patients with Alzheimer's Disease. Mol Neurobiol. 2021; 58(8):4007-4027.
    29. Jiang J, Yang C, Ai JQ, Zhang QL, Cai XL, Tu T, Wan L, Wang XS, Wang H, Pan A, Manavis J, Gai WP, Che C, Tu E, Wang XP, Li ZY, Yan XX. Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation. Front. Aging Neurosci. 2022; 14: 926904
    30. Khurshid B, Rehman AU, Muhammad S, Wadood A, Anwar J. Toward the Noninvasive Diagnosis of Alzheimer's Disease: Molecular Basis for the Specificity of Curcumin for Fibrillar Amyloid-β. ACS Omega. 2022; 7(25):22032-22038.
    31. Lee J, Howard RS, Schneider LS. The Current Landscape of Prevention Trials in Dementia. Neurotherapeutics. 2022; 19(1):228-247.
    32. Liu P, Yang Q, Yu N, Cao Y, Wang X, Wang Z, Qiu WY, Ma C. Phenylalanine Metabolism Is Dysregulated in Human Hippocampus with Alzheimer's Disease Related Pathological Changes. J Alzheimers Dis. 2021; 83(2):609-622.
    33. Ma C, Bao AM, Yan XX, Swaab DF. Progress in Human Brain Banking in China. Neurosci Bull. 2019; 35(2):179-182.
    34. Macklin L, Griffith CM, Cai Y, Rose GM, Yan XX, Patrylo PR. Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline. Exp Gerontol. 2016; 88: 9-18
    35. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985; 82(12):4245-9.
    36. Novak M, Wischik CM, Edwards P, Pannell R, Milstein C. Characterisation of the first monoclonal antibody against the pronase resistant core of the Alzheimer PHF. Prog Clin Biol Res. 1989; 317:755-61.
    37. Ohry A, Buda O. Teofil Simchowicz (1879-1957): the scientist who coined senile plaques in neuropathology. Rom J Morphol Embryol. 2015; 56(4):1545-8.
    38. Oĭfa AI. Paul Divry--founder of the concept of cerebral amyloidosis. Zh Nevropatol Psikhiatr Im S S Korsakova. 1973;73(7):1078-82.
    39. Patel S, Bansoad AV, Singh R, Khatik GL. BACE1: A Key Regulator in Alzheimer's Disease Progression and Current Development of its Inhibitors. Curr Neuropharmacol. 2022; 20(6):1174-1193.
    40. Qiu W, Zhang H, Bao A, Zhu K, Huang Y, Yan X, Zhang J, Zhong C, Shen Y, Zhou J, Zheng X, Zhang L, Shu Y, Tang B, Zhang Z, Wang G, Zhou R, Sun B, Gong C, Duan S, Ma C. Standardized Operational Protocol for Human Brain Banking in China. Neurosci Bull. 2019; 35(2):270-276.
    41. Sasaguri H, Hashimoto S, Watamura N, Sato K, Takamura R, Nagata K, Tsubuki S, Ohshima T, Yoshiki A, Sato K, Kumita W, Sasaki E, Kitazume S, Nilsson P, Winblad B, Saito T, Iwata N, Saido TC. Recent Advances in the Modeling of Alzheimer's Disease. Front Neurosci. 2022; 16:807473.
    42. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer's disease. Lancet. 2021; 397(10284):1577-1590.
    43. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1): a006189.
    44. Shi YB, Tu T, Jiang J, Zhang QL, Ai JQ, Pan A, Manavis J, Tu E, Yan XX. Early Dendritic Dystrophy in Human Brains with Primary Age-Related Tauopathy. Front Aging Neurosci. 2020; 12:596894.
    45. Tahami Monfared AA, Byrnes MJ, White LA, Zhang Q. Alzheimer's Disease: Epidemiology and Clinical Progression. Neurol Ther. 2022; 11(2):553-569.
    46. Tang K, Wan M, Zhang H, Zhang Q, Yang Q, Chen K, Wang N, Zhang D, Qiu W, Ma C. The top 100 most-cited articles citing human brain banking from 1970 to 2020: a bibliometric analysis. Cell Tissue Bank. 2020; 21(4):685-697.
    47. Thal DR, Rüb U, Orantes M, Braak H. Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology. 2002; 58(12):1791-800.
    48. Tu T, Jiang J, Zhang QL, Wan L, Li YN, Pan A, Manavis J, Yan XX. Extracellular Sortilin Proteopathy Relative to β-Amyloid and Tau in Aged and Alzheimer's Disease Human Brains. Front Aging Neurosci. 2020; 12:93.
    49. Wischik CM, Novak M, Thøgersen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988; 85(12):4506-10.
    50. Xiong F, Ge W, Ma C. Quantitative proteomics reveals distinct composition of amyloid plaques in Alzheimer's disease. Alzheimers Dement. 2019; 15(3):429-440.
    51. Xu B, Gao Y, Zhan S, Xiong F, Qiu W, Qian X, Wang T, Wang N, Zhang D, Yang Q, Wang R, Bao X, Dou W, Tian R, Meng S, Gai WP, Huang Y, Yan XX, Ge W, Ma C. Quantitative protein profiling of hippocampus during human aging. Neurobiol Aging. 2016; 39:46-56.
    52. Yan XX, Xiong K, Luo XG, Struble RG, Clough RW. beta-Secretase expression in normal and functionally deprived rat olfactory bulbs: inverse correlation with oxidative metabolic activity. J Comp Neurol. 2007; 501(1):52-69.
    53. Yan XX, Cai Y, Shelton J, Deng SH, Luo XG, Oddo S, Laferla FM, Cai H, Rose GM, Patrylo PR. Chronic temporal lobe epilepsy is associated with enhanced Alzheimer-like neuropathology in 3×Tg-AD mice. PLoS One. 2012;7(11):e48782.
    54. Yan XX, Ma C, Bao AM, Wang XM, Gai WP. Brain banking as a cornerstone of neuroscience in China. Lancet Neurol. 2015; 14(2):136.
    55. Yang W, Guo X, Tu Z, Chen X, Han R, Liu Y, Yan S, Wang Q, Wang Z, Zhao X, Zhang Y, Xiong X, Yang H, Yin P, Wan H, Chen X, Guo J, Yan XX, Liao L, Li S, Li XJ. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis. Protein Cell. 2022; 13(1):26-46.
    56. Zhang L, Jiang Y, Zhu J, Liang H, He X, Qian J, Lin H, Tao Y, Zhu K. Quantitative Assessment of Hippocampal Tau Pathology in AD and PART. J Mol Neurosci. 2020; 70(11):1808-1811.
    57. Zhang X, Sun B, Wang X, Lu H, Shao F, Rozemuller AJM, Liang H, Liu C, Chen J, Huang M, Zhu K. Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy. Neurosci Bull. 2019; 35(2):183-192.
    58. Zhang XM, Cai Y, Xiong K, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Yan XX. Beta-secretase-1 elevation in transgenic mouse models of Alzheimer's disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development. Eur J Neurosci. 2009; 30(12):2271-83.
    59. Zhang Y, Li Y, Ma L. Recent advances in research on Alzheimer's disease in China. J Clin Neurosci. 2020; 81:43-46.
    60. Zhao J, Fu Y, Yasvoina M, Shao P, Hitt B, O'Connor T, Logan S, Maus E, Citron M, Berry R, Binder L, Vassar R. Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer's disease pathogenesis. J Neurosci. 2007; 27(14):3639-49.
    61. Zhou FQ, Jiang J, Griffith CM, Patrylo PR, Cai H, Chu Y, Yan XX. Lack of human-like extracellular sortilin neuropathology in transgenic Alzheimer's disease model mice and macaques. Alzheimers Res Ther. 2018; 10(1):40.
    62. Zhu K, Wang X, Sun B, Wu J, Lu H, Zhang X, Liang H, Zhang D, Liu C. Primary Age-Related Tauopathy in Human Subcortical Nuclei. Front Neurosci. 2019; 13:529.

    How to Cite

    “Characterization of a New Set of Monoclonal β-Amyloid Antibodies ”. Human Brain, vol. 1, no. 1, Oct. 2022, pp. 3-20, https://doi.org/10.37819/hb.001.001.0206.
    ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver
    Download Citation
    Endnote/Zotero/Mendeley (RIS) BibTeX

    How to Cite

    “Characterization of a New Set of Monoclonal β-Amyloid Antibodies ”. Human Brain, vol. 1, no. 1, Oct. 2022, pp. 3-20, https://doi.org/10.37819/hb.001.001.0206.

    HTML
    319

    Total
    321

    Share

    Search Panel

    Huan-Yu Che
    Google Scholar
    Pubmed
    JDMFS Journal

    Jia-Qi Ai
    Google Scholar
    Pubmed
    JDMFS Journal

    Chen Yang
    Google Scholar
    Pubmed
    JDMFS Journal

    Xiao-Lu Cai
    Google Scholar
    Pubmed
    JDMFS Journal

    Yan Wang
    Google Scholar
    Pubmed
    JDMFS Journal

    Juan Jiang
    Google Scholar
    Pubmed
    JDMFS Journal

    Qi-Lei Zhang
    Google Scholar
    Pubmed
    JDMFS Journal

    Tian Tu
    Google Scholar
    Pubmed
    JDMFS Journal

    Ewen Tu
    Google Scholar
    Pubmed
    JDMFS Journal

    Chong Che
    Google Scholar
    Pubmed
    JDMFS Journal

    Xiao-Xin Yan
    Google Scholar
    Pubmed
    JDMFS Journal

    Downloads

    Article Details

    Most Read This Month

    License

    Copyright (c) 2022 Huan-Yu Che, Jia-Qi Ai, Chen Yang, Xiao-Lu Cai, Yan Wang, Juan Jiang, Qi-Lei Zhang, Tian Tu, Ewen Tu, Chong Che, Xiao-Xin Yan

    Creative Commons License

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

    Copyright © 2023 EurAsia Academic Publishing Group. All rights reserved