Amelioration of tau related pathology with a novel anti‐prion protein monoclonal antibody in an AD mouse model. (31st December 2021)

• Record Type: Journal Article
• Authors: Boutajangout, Allal; Zhang, Wei; Abdali, Wed; Kim, Justin Sung Tae; Prelli, Frances; Wisniewski, Thomas
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.054074
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: A number of studies have shown that amyloid β oligomers (Aβo) mediate their toxicity, in part, via the cellular prion protein (PrP C ) on the surface of neurons. We hypothesized that tau oligomers may also mediate toxicity and spread of pathology via PrP C . We have generated a novel monoclonal anti‐PrP antibody (TW1) and assessed the efficacy of passive immunization with this antibody in a mouse model of AD with only tau related pathology. Method: HTau/PS1 transgenic AD model mice were injected at 5 months of age intraperitoneally once a week with TW1 from the age of 5 months. Control mice received only saline. Their behavior was assessed at 8 months of age and brain tissue subsequently harvested for analysis at 9 months Result: The treated and control mice did not show any significant differences in sensorimotor testing. Significant statistical differences were observed with the novel object recognition test in the immunized mice on percentage time spent in zones (two tailed, t‐test p = 0.0019). On the closed field symmetrical maze immunized mice performed significantly better (Day1: two tailed t‐test p=0.0001; Day2: two tailed t‐test p=0.0015; Day3: two tailed t‐test p=0.0002). Fifty percent less tau pathology was observed in the dentate gyrus with PHF‐1 immunolabeling (two tailed t‐test p= 0.02) and a 60% reduction was seen in the piriform cortex (two‐tailed, t‐test p=0.01) in treated vs control animals. CP13 immunolabeling showed a significant difference in the piriform cortex (p=0.02, two‐tailed t‐test) in treated mice versus controls. There was no significant difference in astrogliosis or microgliosis in treated versus control mice. Western blots using PHF‐1 showed that TW1 therapy reduced phosphorylated tau pathology (two‐tailed t‐test p=0.03) and improved the ratio of pathological soluble tau to tubulin (two‐tailed t‐test p=0.0006). The same effect were observed with the CP13 antibody (two‐tailed t‐test p=0.0007) and improved the ratio CP13/tubulin (two tailed, t‐test p=0.0014). Conclusion: These results indicate that passive immunization with the TW1 antibody can significantly decrease tau pathology and improve cognition in a transgenic mouse model of AD.