Tau oligomer antibodies as potential therapeutics for parkinson’s and other synucleinopathies

      Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and with no effective treatments or preventative measures, its prevalence is growing. PD is characterized by cognitive and movement symptoms associated with a loss of dopaminergic neurons, synaptic dysfunction, and the presence of Lewy bodies comprised of α-synuclein. Evidence shows that smaller aggregates, oligomers, may be more toxic. Moreover, we have found that oligomeric α-synuclein coexists with tau protein in disease in a possible toxic synergy, implicating tau oligomers as a therapeutic target for synucleinopathies.
      Objective: Evaluate the efficacy of a tau oligomer-specific antibody (TOMA) in a synucleinopathy mouse model.
      Materials and methods: We treated seven-month-old mice overexpressing A53T mutated α-synuclein intravenously with either TOMA, an antibody for all forms of tau—Tau-13, or a control IgG and wild-type mice with saline. We tested mice on a battery of behavioral tasks assessing memory and motor function. Following testing, half of the mice were sacrificed and tissue was collected for biochemical and immunological analysis. Remaining mice were aged to 12 months and tested again.
      Results: A53T mice treated with TOMA were protected from cognitive and motor deficits, while treating with Tau-13 appeared to exacerbate the phenotype. We found decreased levels of toxic tau oligomers in the brains of TOMA-treated mice. Importantly, levels of dopamine were elevated in TOMA-treated mice, as well as the synaptic protein, Synapsin I.
      Conclusion: Targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable strategy for treating PD.