Regional vulnerability in Alzheimer's disease: The role of cell-autonomous and transneuronal processes

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d409663e142">INTRODUCTION</h5> <p id="P1">The stereotypical progression of Alzheimer’s (AD) pathology is not fully understood. The selective impact of AD on distinct regions has led the field to question if innate vulnerability exists. This study aims to determine if the causative factors of regional vulnerability are dependent on cell-autonomous or transneuronal (non-cell autonomous) processes. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d409663e147">METHODS</h5> <p id="P2">Using mathematical and statistical models, we analyzed the contribution of cell-autonomous and non-cell-autonomous factors to predictive linear models of AD pathology. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d409663e152">RESULTS</h5> <p id="P3">Results indicate gene expression as a weak contributor to predictive linear models of AD. Instead, the Network Diffusion Model acts as a strong predictor for observed AD atrophy and hypometabolism. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d409663e157">DISCUSSION</h5> <p id="P4">We propose a convenient methodology for identifying genes and their role in determining AD topography, in comparison with network-spread. Results reinforce the role of trans-neuronal network spread on disease progression, and suggest innate gene expression plays a secondary role in seeding and subsequent disease progression. </p> </div>