BME 482 Kevin Sylvestre

 35 million cases of Alzheimer’s disease (AD) in U.S. alone  Causes are widely studied  Leading theory- Amyloid Cascade Hypothesis  Mismetabolism of APP leads to aggregation of Amyloid beta (Aβ)  Formation of neuritic plaques  Initiating event in AD

 Peptide of amino acids  Mostly concerned with Aβ42  More fibrillogenic  Formed by cleavage of Amyloid Precursor Protein (APP)  Aβ production follows a circadian rhythm

 Study by Randy L. Buckner, et al “Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer’s Disease”  Identified as areas with disproportionately greater connectivity compared with other regions

 Obvious correlation across 127 samples  Both datasets demonstrate disproportionately high connectivity in same areas  Voxel by voxel comparison; r = 0.93

 Some hubs (A and B) are assosicated with common core network  Others associated with distinct networks (C and D)  A: posterior cingulate  B: dorsolateral pre-frontal cortex  C: Supramarginal gyrus  D: Medial prefrontal cortex

 Hubs maintain activity during both rest fixation and task performance states  Overlaps “default network”

 One can readily observe relation between connectivity (cortical hubs) and Aβ deposition  Formally, shown with visual plotting, and correlation of voxels for each of the values  Conclusion: Aβ deposition occurs preferentially in cortical hubs

 Voxel by voxel comparison  Demonstrates a high correlation  Demonstrates parametric relationship: greater level of functional connectivity across brain, greater level of Aβ deposition in AD

 Cortical hubs maintain activity across task states; may suggest hubs are vulnerable to Aβ deposition due to high, constant baseline activity  APP processing is activity dependant  Neuronal stimulation increases the abundance of Aβ  These conclusions may indicate mechanism for Aβ vulnerability

 Targeted treatment of AD will become possible  Cortical hubs indicate target areas  May provide insight in future treatments of other diseases

 “Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer’s Disease” Randy L. Buckner et. al.; J. Neuroscience. February 11, ULTFORMAT=1&andorexacttitle=and&titleabstract=mapping&andorexacttitleabs=an d&fulltext=Consciousness&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sor tspec=relevance&resourcetype=HWCIT  “Amyloid Cascade Hypothesis” pothesis.html  “Beta amyloid”. (2010, January 28). In Wikipedia, The Free Encyclopedia.  “Alzheimer's Facts and Figures”