On clicking Start Execution button in Plugin Registration Tool for profiling I was getting the AppDomain Unloaded error.
On opening up the error detail the message was
“Could not load file or assembly Microsoft.Xrm.Sdk, Version=5.0.0.0″
Updating the Plugin Project to use the Version 6 assembly that was part of the SDK, from which I was using Plugin Registration tool fixed the issue.
To understand more check the below links
https://crmbusiness.wordpress.com/2015/03/24/crm-2015-understanding-the-plugin-profiler-and-puzzling-error/
https://social.microsoft.com/Forums/en-US/9709c5b3-a035-4c1a-bdd3-6d8054db31d0/profiler-plugin-type-does-not-exist-in-assembly-error?forum=crmdevelopment
http://blogs.msdn.com/b/devkeydet/archive/2015/02/17/debug-crm-online-plugins.aspx
Hope it helps..