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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Immunological memory to hyperphosphorylated tau in asymptomatic individuals
Gabriel Pascual1, Jehangir S Wadia1,2, Xueyong Zhu3
1Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson, 3210, Merryfield Row, San Diego, CA, 92121, USA.
Acta Neuropathologica
|March 26, 2017
Summary
Healthy individuals possess antibodies targeting abnormal tau proteins, suggesting an ongoing immune response. These tau antibodies may serve as Alzheimer's disease biomarkers or therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Antibodies against hyperphosphorylated tau protein have been detected in healthy individuals' serum.
- The specificities and functions of these naturally occurring tau antibodies are not well understood.
Purpose of the Study:
- To characterize the specificities of antibodies from healthy individuals that bind to phosphorylated tau peptides.
- To evaluate the therapeutic potential of these identified tau antibodies.
Main Methods:
- Single-cell screening of peripheral IgG+ memory B cells from asymptomatic donors.
- Recovery, cloning, and expression of antibody sequences as full-length IgGs.
- In vitro tau aggregation inhibition assays and immunohistochemistry on post-mortem brain tissue.
Main Results:
- 52 somatically mutated tau-binding antibodies were identified, belonging to 35 unique clonal families.
- 26 antibodies showed phosphorylation-dependent binding; 13 inhibited tau aggregation in vitro.
- Two antibodies, CBTAU-7.1 and CBTAU-22.1, detected pathological tau in brain tissue.
Conclusions:
- The human immune system mounts a response against pathological tau, even in the absence of Alzheimer's disease symptoms.
- The identified tau antibodies demonstrate potential as diagnostic biomarkers or therapeutic agents for Alzheimer's disease.
