Affiliations: [a]
Tokyo Metropolitan Institute of Medical Sciences, Setagaya-ku, Tokyo, Japan
| [b] Division of Animal Sciences, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan
| [c]
Department of Physiology, Nippon Medical School, Tokyo, Japan
Correspondence:
[*]
Correspondence to: Dr. Makoto Hashimoto, Tokyo Metropolitan Institute of Medical Sciences, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-0057, Japan. Tel.: +81 3 6834 2354; Fax: +81 3 5316 3150; E-mail: hashimoto-mk@igakuken.or.jp.
Abstract: Recent clinical trials using immunization approaches against Alzheimer’s disease (AD) have failed to demonstrate improved cognitive functions in patients, despite potent suppression in the formation of both senile plaques and other amyloid-β deposits in postmortem brains. Similarly, we observed that treatment with ibuprofen, a non-steroidal anti-inflammatory drug, was effective in improving the histopathology, such as reducing both protein aggregation and glial activation, in the brains of transgenic mice expressing dementia with Lewy bodies-linked P123H β-synuclein. In contrast, only a small improvement in cognitive functions was observed in these mice. Collectively, it is predicted that histology does not correlate with behavior that is resilient and resistant to therapeutic stimuli. Notably, such a ‘discrepancy between histology and behavior’ is reminiscent of AD-like pathologies and incidental Lewy bodies, which are frequently encountered in postmortem brains of the elderly who had been asymptomatic for memory loss and Parkinsonism during their lives. We suggest that ‘the discrepancy between histology and behavior’ may be a universal feature that is associated with various aspects of neurodegenerative diseases. Furthermore, given that the cognitive reserve is specifically observed in human brains, human behavior may be evolutionally distinct from that in other animals, thus, contributing to the differential efficiency of therapy between human and lower animals, an important issue in the therapy of neurodegenerative diseases. Overall, it is important to better understand ‘the discrepancy between histology and behavior’ in the mechanism of neurodegeneration for the development of effective therapies against neurodegenerative diseases.
