Likewise, a comprehensive study of hippocampal CA1 pyramidal neurons also demonstrated that autophagy increases in early-stage AD (Braak stage III) and subsequently decreases in late-stage (Braak stage V), reflected by the accumulation of LC3-II and SQSTM1/p61 and increased autolysosomal size and total area [25]. This evidence concerns the gene SQSTM1 and Alzheimer disease.