Understanding the relationship between neuroinflammatory cells and AD-related symptoms through systems genetics.

Michelle Kung

Document Type

Article

Publication Date

Summer 2017

JAX Location

In: Student Reports, Summer 2017, Jackson Laboratory

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by two classical pathological hallmarks (AJ3 plaques and hyperphosphorylated tau protein), as well as a decline in cognitive abilities (1). However, recent studies have demonstrated that levels of these pathologies do not always correlate with the degree of cognitive decline- leading to the speculation that other factors, including neuroinflammatory glia, playa more casual role in the disease. The purpose of this study is to determine if the quantities of either astrocytes, microglia or neurons are more highly predictive of cognitive performance in AD models than AJ3 pathology. We have hypothesized that these neuroinflammatory glia are more highly correlated with cognitive function in AD than traditional neuropathologies such as AJ3 plaques. Using Image J and CeliProfiler, the number of astrocytes in the cerebral cortex was measured across a genetically-diverse panel of AD mice, and these quantitative traits (e.g. cell number and percent brain area covered) were compared to cognitive performance, thus allowing for the assessment of the relationship between cognitive function and cell quantities. As a result, astrocyte counts and areas were found to be associated with AD human mutations, as astrocyte quantities were much lower in non-mutants than in ADmutants. Despite this, there was poor correlation between astrocyte densities and cognitive performance. Further analysis of other glia densities in brain sections across the panel of mice may allow for more significant and conclusive results.

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