Early Aβ-HBc virus-like particles immunization had better effects on preventing the deficit of learning and memory abilities and reducing cerebral Aβ load in PDAPP mice

Abstract

For nearly two decades, immunization against the β-amyloid peptide (Aβ) has been investigated as a potential treatment for Alzheimer’s disease (AD). Despite some disappointing results in clinic trials, greater significance has been attached by some researchers to exploring the immune effects on pathological and cognitive changes in AD or producing new vaccines of AD. In the previous study, we have made a virus-like particles (Aβ-HBc VLPs) as Aβ vaccine candidate. Aβ-HBc VLPs could ameliorate the learning and memory abilities and reduce cerebral Aβ deposit in the old PDAPP mice. In the present study, to observe the preventive effect and the proper time of immunization, 3, 6 and 9-month old PDAPP mice were immunized with Aβ-HBc VLPs for 3 months. All mice generated high titer of anti-Aβ antibody after Aβ-HBc VLPs immunizations. When the mice were 15-month old, Morris Water Maze was used to test their learning and memory abilities. The escape latencies of Aβ-HBc VLPs immunized mice were shorter than that of control mice. These immunized mice entered platform region frequently and spent more time on the platform region and quadrant. 3 m and 6 m Aβ-HBc VLPs immunized groups performed better than the 9 m group. In immunohistochemistry tests, all the Aβ-HBc VLPs immunized mice had less amyloid deposit in cortex and hippocampus. ELISA results showed that soluble Aβ was reduced in the brain homogenates of the Aβ-HBc VLPs immunized mice, and 3- and 6-month groups had less soluble Aβ than the 9-month group. In conclusion, our study showed that Aβ-HBc VLPs immunization could elicit a strong immune response in adult APP mice, and early immunization had better effects on preventing learning and memory deficits, lowering Aβ burden in PDAPP mice.