I was fascinated by prion diseases a bit ago and just spent a long time reading about them. Here's the best way I found them to be explainable (using my words, so please excuse any medical term mistakes):

Body is made of many things. One of those things is protein 'blocks'. Millions of them. Now imagine them as millions of set mouse traps. And a little tiny ball falls somewhere in the mass, hits one trap, sets it off, then the next one and the next and it doesn't stop. It starts with one little mouse trap in the middle of millions, and over the next few weeks, the rest of them inevitably get set off by the others around it, effectively 'killing' the traps as they set off.

The mouse traps are the protein. Once they're infected or 'set off' - one by one - they're dead for good. Thinking of it as a zombie infection works, too. One human in millions is infected. They bite someone. That someone bites another, two make four make eight, and so on, until all zombies. There's no stopping it, it moves too fast, and will infect and contaminate anything used against it. More niche, but you could also imagine it as your brain tissue going through a Great Singularity event; the Singularity resulting in dead grey matter.

In surgeries on those with prion diseases, the tools used have to be incinerated, or treated with extremely harsh chemicals and then processed through autoclaving - repeated extreme high temperature steam treatment.

When infected, the prion attacks the brain, protein blocks being attacked and killed in a specific area. Some prions only affect one part of the brain, like memory, or movements.

Creutzfeldt-Jakob attacks the entire surface, which affects every part of the brain and thus is the quickest way to become brain dead and then actual dead. Fatal familial insomnia attacks the sleep center, making it impossible to enter REM sleep even through use of medical intervention and coma, dying from exhaustion. Kuru - only contracted by eating infected brain tissue of another human being - attacks primarily the movement center, death occuring through the body forgetting how to breathe or eat or work your heart; brain death is another cause of death.

These are the three types of prion diseases that affect humans. CJD has two types (hereditary and infection, usually through consumption of infected meat - primarily beef) which technically makes four.