TY - JOUR T1 - Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease A1 - de Haan, Willem A1 - Mott, Katherine A1 - van Straaten, Elisabeth C. W. A1 - Scheltens, Philip A1 - Stam, Cornelis J. Y1 - 2012/08/16 N2 - Author Summary An intriguing recent observation is that deposition of the amyloid-β protein, one of the hallmarks of Alzheimer's disease, mainly occurs in brain regions that are highly connected to other regions. To test the hypothesis that these ‘hub’ regions are more vulnerable due to a higher neuronal activity level, we examined the relation between brain connectivity and activity in a computational model of the human brain. Furthermore, we simulated progressive damage to brain regions based on their level of activity, and investigated its effect on the structure and dynamics of the remaining brain network. We show that brain hub regions are indeed the most active ones, and that by damaging networks according to regional activity levels, we can reproduce not only hub vulnerability but a range of phenomena encountered in actual neurophysiological data of Alzheimer patients as well: loss and slowing of brain activity in Alzheimer, loss of synchronization between areas, and similar changes in functional network organization. The results of this study suggest that excessive, connectivity dependent neuronal activity plays a role in the development of Alzheimer, and that the further investigation of factors regulating regional brain activity might help detect, elucidate and counter the disease mechanism. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 8 IS - 8 UR - https://doi.org/10.1371/journal.pcbi.1002582 SP - e1002582 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002582 ER -