Isolation and characterization of antibody fragments selective for toxic oligomeric tau

Huilai Tian, Eliot Davidowitz, Patricia Lopez, Ping He, Philip Schulz, James Moe, Michael Sierks

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Oligomeric tau species are important in the onset and progression of Alzheimer's disease (AD), as they are neurotoxic and can propagate tau-tangle pathology. Therefore, reagents that selectively recognize different key morphologies of tau are needed to help define the role of tau in AD and related diseases. We utilized a biopanning protocol that combines the binding diversity of phage-displayed antibody libraries with the powerful imaging capability of atomic force microscopy to isolate single-chain antibody fragments (scFvs) that selectively bind toxic oligomeric tau. We isolated 3 different antibody fragments that bind oligomeric but not monomeric or fibrillar tau. The scFvs differentiate brain tissue homogenates of both 3×TG and tau-AD mice from wild-type mice, detecting oligomeric tau at much earlier ages than when neurofibrillary tangles are typically detected. The scFvs also distinguish human postmortem AD brain tissue from cognitively normal postmortem human brain tissue, demonstrating the potential of this approach for developing biomarkers for early detection and progression of AD.

Original languageEnglish (US)
Pages (from-to)1342-1355
Number of pages14
JournalNeurobiology of Aging
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2015

    Fingerprint

Keywords

  • Alzheimer's disease
  • Antibody fragments
  • Biomarker
  • Brain tissue
  • Immunotherapy
  • Oligomeric tau
  • Phage display
  • ScFv
  • Toxic tau aggregates

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this