1. BME 482 Kevin Sylvestre

2.  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

3.  Peptide of 39-43 amino acids  Mostly concerned with Aβ42  More fibrillogenic  Formed by cleavage of Amyloid Precursor Protein (APP)  Aβ production follows a circadian rhythm

4.  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

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

7.  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

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

9.  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

11.  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

12.  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

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

14.  “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, 2009 http://www.jneurosci.org/cgi/reprint/29/6/1860?maxtoshow=&HITS=10&hits=10&RES 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” http://wiki.iop.kcl.ac.uk/default.aspx/Neurodegeneration/Amyloid%20Cascade%20Hy pothesis.html  “Beta amyloid”. (2010, January 28). In Wikipedia, The Free Encyclopedia. http://en.wikipedia.org/w/index.php?title=Beta_amyloid&oldid=340508037  “Alzheimer's Facts and Figures” http://www.alz.org/alzheimers_disease_facts_figures.asp