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Antibody-derived in vivo imaging of tau pathology
#MMPMID25505335
Krishnaswamy S
; Lin Y
; Rajamohamedsait WJ
; Rajamohamedsait HB
; Krishnamurthy P
; Sigurdsson EM
J Neurosci
2014[Dec]; 34
(50
): 16835-50
PMID25505335
show ga
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-? 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.
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