Abstract
Recent work from our lab and few others have strongly suggested that immunotherapy could be an effective means of preventing the development of tau accumulation in JNPL3 transgenic mice, carrying the human P301L mutation. The aim of this study was to test the efficacy of a variety of specific tau monoclonal antibodies in JNPL3. Starting at 3 months of age, mice were treated for 4 months with weekly intraperitoneal injections of saline or purified tau monoclonal antibodies (10mg/Kg) different in specificity for pathological tau: CP13 (pSer202), RZ3 (pThr231) and PG5 (pSer409). As expected, not all the antibodies tested showed efficacy at preventing the development of tau pathology at the described dose, with some of them even worsening the pathological scenario. Only by targeting the pSer202 epitope with CP13 was a conspicuous reduction of insoluble or soluble tau in cortex and hindbrain obtained. Here we report about the importance of screening in vivo multiple tau antibodies in order to select the antibodies to direct into future clinical studies.
Highlights
Alzheimer’s disease accounts for 50–80% of senile dementias
Tau pathology progresses in a predictable manner, going from one brain region to another according to a disease-specific pattern [1,2,3,4,5]
Analysis of the insoluble fractions revealed that CP13 was the only antibody able to effectively decrease tau pathology
Summary
In AD, neurofibrillary tangles (NFT) together with amyloid plaques and neuronal loss characterize brain pathology. The link between the two lesions is still unknown but the severity of the cognitive deficit appears to closely correlate with the amount and extent of NFT pathology. Tau pathology progresses in a predictable manner, going from one brain region to another according to a disease-specific pattern [1,2,3,4,5]. The “conventional” evolution pattern of tau lesions has been described with abnormal and hyperphosphorylated tau initially appearing in a non-fibrillar and non-argyrophilic form that is soluble to some degree in the neuronal cytoplasm and is referred to as “pretangle” material. Recent findings have shown that “extracellular tau” might be the culprit in propagation of tau pathology as disease progresses. The molecular nature of PLOS ONE | DOI:10.1371/journal.pone.0135774 August 13, 2015
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