| Title |
Immunological memory to hyperphosphorylated tau in asymptomatic individuals
|
|---|---|
| Published in |
Acta Neuropathologica, March 2017
|
| DOI | 10.1007/s00401-017-1705-y |
| Pubmed ID | |
| Authors |
Gabriel Pascual, Jehangir S. Wadia, Xueyong Zhu, Elissa Keogh, Başak Kükrer, Jeroen van Ameijde, Hanna Inganäs, Berdien Siregar, Gerrard Perdok, Otto Diefenbach, Tariq Nahar, Imke Sprengers, Martin H. Koldijk, Els C. Brinkman-van der Linden, Laura A. Peferoen, Heng Zhang, Wenli Yu, Xinyi Li, Michelle Wagner, Veronica Moreno, Julie Kim, Martha Costa, Kiana West, Zara Fulton, Lucy Chammas, Nancy Luckashenak, Lauren Fletcher, Trevin Holland, Carrie Arnold, R. Anthony Williamson, Jeroen J. Hoozemans, Adrian Apetri, Frederique Bard, Ian A. Wilson, Wouter Koudstaal, Jaap Goudsmit |
| Abstract |
Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG(+) memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 54 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 22% |
| Student > Ph. D. Student | 10 | 19% |
| Student > Bachelor | 5 | 9% |
| Other | 4 | 7% |
| Student > Postgraduate | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 16 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 10 | 19% |
| Neuroscience | 10 | 19% |
| Medicine and Dentistry | 6 | 11% |
| Agricultural and Biological Sciences | 2 | 4% |
| Nursing and Health Professions | 1 | 2% |
| Other | 6 | 11% |
| Unknown | 19 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 22. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 February 2023.
All research outputs
#1,698,438
of 25,220,525 outputs
Outputs from Acta Neuropathologica
#327
of 2,529 outputs
Outputs of similar age
#32,335
of 315,103 outputs
Outputs of similar age from Acta Neuropathologica
#11
of 34 outputs
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