The Berlin Zoo said in a statement that a preliminary necropsy conducted Monday revealed "significant changes to the brain, which could be seen as the reason for the sudden death of the polar bear."
It said no other organ damage had been identified but that the examination was continuing.
Knut was found lifeless in the pool in his enclosure on Saturday afternoon. An amateur video showing Knut's final moments has been posted to the internet. After walking in repetitive circles for some time, he seems to have a seizure before collapsing into the water in his enclosure.
The video could be disturbing to some people.
Knut shot to fame as a cuddly cub after being abandoned by his mother and reared by hand.
Devastated fans have been leaving flower bouquets, written tributes and photos of Knut at his former den at the zoo, while an online condolence book has drawn more than 4,000 messages.
Meanwhile, a fan organisation started collecting donations for a memorial to the bear.
"Knut will live on in the hearts of many visitors but we want to create something lasting for generations to come with this memorial so that the uniqueness of this animal personality will endure," the chairman of the Friends of the Capital Zoo, Thomas Ziolko, said.