SQSTM1 and Alzheimer disease: In a hereditary form of AD, it was shown that a mutation in the PSEN1 gene encoding for transmembrane protein presenilin 1, a component of the gamma-secretase complex, leads to abnormal alkalization of lysosomes, a decrease in lysosomal hydrolase activity, and an increase in p62 levels, findings that are consistent with impaired lysosomal degradation [45].