Intraperitoneal Administration of Monoclonal Antibody Against Pathologic Aβ42 Aggregates Alleviated Cognitive Deficits and Synaptic Lesions in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common form of dementia, characterized by amyloid-beta peptide (Abeta) aggregates, phosphorylated tau protein (p-tau), and progressive neurodegeneration. Amyloid-beta peptide 42 (Abeta42) is considered an early trigger of AD pathogenesis. We have previously reported that Abeta N-terminus monoclonal antibody (mAb) A8 alleviated cognitive dysfunction and reduced the abundance of soluble Abeta in the brains of the senescence-accelerated mouse prone 8 (SAMP8) mouse model. To confirm the efficacy of mAb A8 in the double-transgenic APPswe/PS1DeltaE9 (APP/PS1) mice, here we reported the related findings. The Morris water maze (MWM) data showed that the A8 treatment group had a shorter escape latency than the control groups in the place navigation test and the probe trial (p < 0.05). Moreover, immunohistochemistry showed decreased levels of both Abeta and p-tau in the brains of APP/PS1 mice. Regarding Abeta levels, western blot results showed that Abeta42 oligomer (p < 0.01) but not Abeta40 levels were diminished in brains of A8-treated APP/PS1 mice. Western blot results showed that phospho-tau (pSer231) (p < 0.01) but not tau levels were reduced in A8-treated mouse brains. Furthermore, transmission electron microscopy images indicated ultrastructural improvements, including an increased (p < 0.01) density of synapses and a reduction of abnormally enlarged mitochondria (p < 0.01), in the brains of A8-treated mice. Taken together, our data showed that mAb A8 is highly efficacious in APP/PS1 mice as a treatment for AD, and the underlying mechanism may target synaptic pathology by inhibiting the amyloid cascade.