Cool to see F# here! Emulators are a great way to learn a language. On first sight you chose well between more or less idiomatic F# for each job.
Some low hanging fruit to reduce allocations: the discriminated unions in Instructions.fs could be [<Struct>], reusing field names to reuse internal fields.
Also, minor nitpick but I'm confused about some of the registers. They are already of type byte, the setters with `a &&& 0xFFuy` don't add anything over `member val A = 0uy with get, set`. I'm guessing this changed over time.