Antibodies directed to the phospho-tau peptide (residues 111-137) dissociate tau oligomers and reduce the spatial memory deficits in non-transgenic tauopathy model rats

Subramanian, Sarada ; Savanur, Ganesh

Abstract

In dementia, Alzheimer’s disease (AD) is the most common type, characterized by the deposits of neurofibrillary tangles and senile plaques with concomitant deterioration in spatial memory and other cognitive functions. Till date, although no cure is available for AD, a few treatment options offer help in reducing the symptoms. In the present study, the sequence 111-137 in the distal N-terminal charge transition region of tau, harbouring the pathologically relevant phospho-serine (pSer 113) and phospho-threonine (pThr 123) (111TPpSLEDEAAGHVpTQARMVSKSKD GTGS137)was selected as a potential immunotherapeutic peptide. Polyclonal anti-peptide antibodies raised in rabbits effectively dissociated the oligomers/aggregates of recombinant human tau in vitro. Administration of affinity purified anti-peptide antibodies to the okadaic acid induced tauopathy model rats resulted in a significant progress in spatial memory functions in Barnes maze task with concomitant reduction in p-tau levels in the hippocampal homogenates. Thus, targeting the phospho-residue sequence 111-137 in tau may be therapeutically relevant for AD and other related tauopathies. These antibodies may also have a clinical value in terms of immunosassay development for quantitation of pathology associated pSer113 and pThr 123 in AD samples.


Keyword(s)

Alzheimer disease, Barnes maze, Dementia, Okadaic acid

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