However, many of these studies, e.g., in APP/PS1 mice, encounter specific limitations: (i) female and male animals were pooled (in a balanced or unbalanced way) and were not investigated in a sex-specific manner or there was no information provided about the sex distribution [37–40], (ii) only one sex (generally males) was studied [41–43], (iii) the entire brain was investigated and not individual BROIs, although different brain regions can be differentially affected by AD pathogenesis [38]. This evidence concerns the gene APP and Alzheimer disease.