Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region
Abstract
:1. Introduction
2. Materials and Methods
2.1. Generation of Novel Anti-Aβ Mouse Monoclonal Antibody
2.2. Antibodies
2.3. Tissue Processing and Immunohistochemistry
2.4. Quantification of Aβ Plaques in Human Brain Tissue
2.5. Enzyme-Linked Immunosorbent Assay (ELISA)
2.6. Calcium Phosphate Transfection and Cell Harvest
2.7. Western Blotting
3. Results
3.1. Epitope Characterization of Novel Monoclonal Antibody 3C11
3.2. Immunohistochemical Staining of Aβ Pathology Using Novel Monoclonal Antibody 3C11
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide | Primary Amino Acid Sequence |
---|---|
Aβ 1–12 | DAEFRHDSGYEV |
Aβ 2–14 | AEFRHDSGYEVHH |
Aβ 4–16 | FRHDSGYEVHHQK |
Aβ 1–16 | DAEFRHDSGYEVHHQK |
Aβ 6–18 | HDSGYEVHHQKLV |
Aβ 8–20 | SGYEVHHQKLVFF |
Aβ 1–20 | DAEFRHDSGYEVHHQKLVFF |
Aβ 1–28 | DAEFRHDSGYEVHHQKLVFFAEDVGSNK |
Aβ 17–24 | LVFFAEDV |
Aβ 23–42 | DVGSNKGAIIGLMVGGVVIA |
Aβ 11-42 | EVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA |
Aβ 1–40 | DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVV |
Aβ 1–42 | DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA |
Cases | Primary Neuropathological Diagnosis | Secondary Neuropathological Diagnosis | Tertiary Neuropathological Diagnosis | Thal Phase | Braak Stage | CERAD | APOE | Sex | Age |
---|---|---|---|---|---|---|---|---|---|
AD-1 | AD high | CAA widespread, mild to moderate | LATE stage 2 | 4 | VI | Frequent | 3/4 | f | 82 |
AD-2 | AD high | CAA widespread, moderate | 5 | VI | Frequent | 4/4 | m | 70 | |
AD-3 | AD high | CAA widespread, moderate | LBD amygdala predominant | 5 | V | Frequent | 3/3 | f | 82 |
AD-4 | AD high | CAA widespread, moderate | 5 | VI | Frequent | 4/4 | m | 72 | |
AD-5 | AD high | CAA, moderate, widespread | 5 | V | Frequent | 3/4 | f | 86 | |
AD-6 | AD high | CAA widespread, moderate | LATE NC stage 2, hippocampal sclerosis | 4 | V | Frequent | 3/4 | f | 87 |
AD-7 | AD high | CAA widespread, moderate | 5 | V | Frequent | 3/3 | f | 78 | |
AD-8 | AD high | CAA widespread, moderate | LBD limbic-transitional | 5 | VI | Frequent | 3/3 | f | 81 |
AD-9 | AD high | CAA widespread, moderate | LATE stage 1 | 5 | V | Frequent | 4/4 | f | 71 |
AD-10 | AD high | CAA widespread, moderate | 5 | VI | Frequent | 3/4 | m | 63 | |
AD-11 | AD high | CAA focal, mild | 5 | V | Frequent | 3/4 | f | 85 | |
AD-12 | AD high | CAA widespread, moderate to severe | 3 | V | Frequent | 4/4 | f | 82 | |
AD-13 | AD high | LBD diffuse neocortical | 5 | VI | Frequent | 3/4 | f | 84 | |
AD-14 | AD high | CAA widespread, moderate to severe | cortical microinfarcts | 5 | V | Frequent | 3/4 | f | 85 |
AD-15 | AD high | CAA widespread, moderate to severe | 5 | V | Frequent | 3/4 | m | 80 | |
AD-16 | AD high | CAA widespread, mild to moderate | 5 | V | Frequent | 3/3 | f | 83 | |
AD-17 | AD high | 5 | VI | Frequent | 3/3 | f | 76 | ||
AD-18 | AD high | CAA widespread, moderate | LATE NC stage 2, hippocampal sclerosis | 5 | VI | Frequent | 3/4 | f | 99 |
AD-19 | AD high | CAA (moderate) | LATE NC 1 | 5 | VI | Frequent | 3/4 | m | 81 |
AD-20 | AD high | CAA widespread, mild | LBD limbic-transitional | 5 | VI | Frequent | 4/4 | f | 76 |
AD-21 | AD high | LBD amygdala predominant | CAA focal, mild | 5 | VI | Frequent | 4/4 | f | 75 |
AD-22 | AD high | LBD amygdala predominant | CAA focal, mild | 5 | VI | Frequent | 3/3 | m | 70 |
AD-23 | AD high | CAA widespread, mild to moderate | LBD amygdala predominant | 5 | VI | Frequent | 3/3 | m | 78 |
AD-24 | AD high | LBD amygdala predominant | 5 | V | Frequent | 3/3 | f | 88 | |
Control-1 | PART, definite, Braak II | 0 | II | None | 3/3 | f | 72 | ||
Control-2 | No significant pathological findings | 0 | 0 | None | 3/4 | f | 55 | ||
Control-3 | PART, definite, Braak I | 0 | I | None | 2/3 | f | 73 |
Case | 3C11/Ab5 Immunoreactive Positivity of Dense Aβ Plaques |
---|---|
AD-1 | 0.55 |
AD-2 | 0.92 |
AD-4 | 0.52 |
AD-7 | 0.90 |
AD-8 | 0.86 |
AD-10 | 0.85 |
AD-11 | 0.98 |
AD-20 | 0.60 |
AD-21 | 1.32 |
AD-22 | 1.10 |
AD-23 | 0.60 |
AD-24 | 0.51 |
N | 12 |
Mean of all cases (Standard deviation) | 0.81 ± 0.26 |
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Paterno, G.; Moore, B.D.; Bell, B.M.; Gorion, K.-M.M.; Ran, Y.; Prokop, S.; Golde, T.E.; Giasson, B.I. Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region. Antibodies 2024, 13, 68. https://doi.org/10.3390/antib13030068
Paterno G, Moore BD, Bell BM, Gorion K-MM, Ran Y, Prokop S, Golde TE, Giasson BI. Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region. Antibodies. 2024; 13(3):68. https://doi.org/10.3390/antib13030068
Chicago/Turabian StylePaterno, Giavanna, Brenda D. Moore, Brach M. Bell, Kimberly-Marie M. Gorion, Yong Ran, Stefan Prokop, Todd E. Golde, and Benoit I. Giasson. 2024. "Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region" Antibodies 13, no. 3: 68. https://doi.org/10.3390/antib13030068