About 70% of them, it took me a while to figure out which ones do

There's a mutation in an enzyme that cleaves a protein called amyloid beta, amyloid beta is necessary for the brain and a part of normal physiological function when investigated in KO mice. In AD the protein starts cleaving AB into a toxic form AB42, as the ratio of this to healthy AB begins to shift aggregates build. Many things happen from here, you get resident immune cells trying to dispose of these building aggregates which can make things worse if they're not cleared via the CSF. Eventually this build up can cause problems with the neurovascular unit and the blood brain barrier meaning cells aren't supplied correctly and you see increases in for the sake of simplicity what I'll call toxins. These again cause cell death, this further contributes to toxic build up you start to get inflammatory responses which again make things worse and this cascade just keeps going. I've just finished my PhD thesis on brain inflammation at the BBB. There's still a huge amount we don't know but when I was growing 3D human cortical spheroids and staining them we did see breakdown of the synapses in particular when AD models were compared to controls. There's a lot left to learn about AD and many mechanisms just aren't fully understood.