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O4‐04–05: Accelaration of familial Alzheimer's disease by homocysteic acid and recovery from neuropathology by anti‐homocysteic acid antibody
Author(s) -
Hasegawa Tohru
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.531
Subject(s) - hippocampus , neuropathology , medicine , saline , endocrinology , memory impairment , chemistry , disease , psychiatry , cognition
received the first 3 injections every 2 weeks and then at monthly intervals. At 7-8 months, the mice went through extensive behavioral testing to determine treatment efficacy and were then killed at 8-9 months for analysis. Results: The immunogen elicited an IgM/IgG response and the therapy prevented cognitive decline in three different tests: Radial Arm Maze (p 0.01-0.001); Closed Field Symmetrical Maze (p 0.01-0.001), and; Object Recognition Test (p 0.01). The groups performed equally well in motor tests indicating that motor deficits were not a confounding variable, which further strengthens our results. Tau/tangle aggregates were reduced by 56% in the pyriform cortex (p 0.01) in the immunized mice. Analysis is underway of other brain regions as well as of levels of soluble and insoluble tau protein. Importantly, the cognitive improvements correlated well with reduction of tau aggregates. In the Radial Arm Maze, correlation was observed in days 4-9 as the mice improve at navigating the maze (p 0.05-0.001). Likewise, in the Closed Field Symmetrical Maze, correlation was only observed in the most complex maze (Maze C, p 0.01), and not in the Object Recognition Test, which is a simpler task. Conclusions: Overall, our findings support the feasibility of immunotherapy targeting pathological tau as a potential treatment for Alzheimer’s disease. Supported by: AG20197.