Maybe a jealous rival from Ash's past who has been biding their time. They could befriend Leaf and slowly turn her against Ash by filling her head with lies about how Ash has always been one - step ahead of them unfairly. This would make the rival the main antagonist driving the betrayal plot.
It could be a new and powerful trainer who has a vendetta against Ash. This trainer might see Ash as a threat to their own rise to the top in the Pokemon world. They could manipulate Leaf into betraying Ash to further their own goals.
An evil Pokemon organization, like Team Rocket but more menacing, could be the main antagonist. They might target Ash because of his unique bond with his Pokemon. They could use Leaf's insecurities or desires to make her betray Ash, for example, by offering her a powerful Pokemon in exchange for her cooperation.