title: Antibody-derived in vivo imaging of tau pathology.
abstract: Antibodies or their derivatives as imaging probes for pathological tau protein have great potential, but have not been well studied. In particular, smaller, single-chain-variable antibody fragments (scFv's) are attractive for detecting tau lesions in live subjects. Here, we generated libraries of scFv's and identified numerous phospho-tau-selective scFv's. Peripheral injection of one of these scFv's consistently resulted in a strong in vivo brain signal in transgenic tauopathy mice, but not in wild-type or amyloid-β plaque mice. The parent tau antibody provided similar results, albeit with a weaker signal intensity. The imaging signal correlated very well with colocalization of the probe with intraneuronal tau aggregates. Both were associated with markers of endosomes, autophagosomes, and lysosomes, suggesting their interaction in these degradation pathways. Such specific antibody-derived imaging probes have great potential as diagnostic markers for Alzheimer's disease and related tauopathies.
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Krishnaswamy
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Wajitha J
authors.initials: WJ
authors.lastname: Rajamohamedsait
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Hameetha B
authors.initials: HB
authors.lastname: Rajamohamedsait
authors.affiliation: Department of Neuroscience and Physiology and.
authors.forename: Pavan
authors.initials: P
authors.lastname: Krishnamurthy
authors.affiliation: Department of Neuroscience and Physiology and Department of Psychiatry, New York University School of Medicine, New York, New York 10016 Einar.Sigurdsson@nyumc.org.
authors.forename: Einar M
authors.initials: EM
authors.lastname: Sigurdsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D057127:Single-Chain Antibodies; D016875:tau Proteins
keywords: Alzheimer's disease; IVIS; diagnosis; imaging; scFv; tau