Alphas are creations of Eve, and represent a line of monsters, making them the first of their kind.
Known Alphas
In The Show
6.02 - Two And A Half Men
The Alpha Shapeshifter appears before the Campbells to retrieve a baby Shapeshifter, it was immune to everything the Campbells had to throw at it and was able to defeat the Campbells easily.
6.05 - Live Free or Twihard
The Alpha Vampire showed all Vampires of the nest Dean was currently occupying a vision of his location so that his army could gather to him.
6.07 - Family Matters
The Alpha Vampire is kidnapped and taken by Samuel and Christian for interrogation, it reveals Samuels motives of locating Purgatory. It seemed very interested in the fact that Sam had no soul. It escaped the Campbell's custody and snapped Christian's neck in a fight. It was about to blood Sam when Christian injected it with Dead Man's Blood, which weakened it and he and The Alpha dissappeared. Although snapping Christian's neck had no effect on the demon that was currently possessing him, the Alpha killed the actual Christian.
6.08 - All Dogs Go To Heaven
The Alpha Skinwalker rallies an army of Skinwalkers who are ordered to turn the families of the pets they are posing as when directed, killing the Alpha is Sam and Dean's only hope of stopping the massacre.
6.10 - Caged Heat
The Alpha Shapeshifter appears in the beginning of the episode taking the form of Crowley's host. He was being tortured by Crowley and was killed by a beheading because he wouldn't tell him the location of Purgatory. We learn in this episode that weapons made of iridium are capable of killing the Alpha Shapeshifter.