Moreover, MAM are particularly sensitive to the neurodegenerative process since treatment of neurons with Aβ affects ER–mitochondria contacts; alterations of ER–mitochondria association and function are seen in APP transgenic mouse models; and small interfering RNA knockdown of MAM proteins (S1R, phosphofurin acidic cluster sorting protein-2) results in neurodegeneration while MAM proteins are upregulated in AD mouse models95. This evidence concerns the gene APP and Alzheimer disease.