Of note, <i>PSEN1</i> mutation induces accumulation and clustering of lysosomes that, along with an increase of global p62/SQSTM1, could compromise lysosomal function and, ultimately, its degradation.<h4>Conclusion</h4>The findings suggest that all these modifications could eventually contribute to the neuronal degeneration that underlies the pathogenesis of Alzheimer's disease. This evidence concerns the gene SQSTM1 and early-onset autosomal dominant Alzheimer disease.