Improvement of neuropathology methods for integrative studies on neurodegenerative diseases in human brains

Despite a massive research effort to elucidate neurodegenerative diseases in recent decades, effective treatment remains elusive. This failure may relate to an oversimplification of the pathogenic processes underlying neurodegenerative diseases and also lack of understanding of neurodegenerative diseases progression during their long latent stages.

Although evidence shows that the two specific neuropathological hallmarks in neurodegenerative diseases (neuronal loss and protein accumulation), which are opposite in nature, do not progress in parallel, the great majority of studies have focused on only one of these aspects, regardless of the disease. Furthermore, research focusing on single brain structures is likely to render an incomplete picture of neurodegenerative disease pathogenesis because as neurodegenerative diseases involve complete brain networks, potential compensatory mechanisms within the network may ameliorate impairment of the system to a certain extent. The Grinberg lab has been developing and improving neuropathological methods for enabling integrative analysis of the dual nature neurodegenerative disease’s lesions, simultaneously, in all components of one of the most vulnerable brain networks.

This approach combines unbiased stereology with immunohistochemistry and immunofluorescence, making use of advanced graphics computing for three-dimensional (3D) volume reconstructions. Using this approach a significant number of cases can be processed and analyzed within a funding cycle, enabling data analysis in a short period of time, It represents a considerable improvement to past low-throughput methods.