Morphometric Similarity Patterning of Amyloid-β and Tau Proteins Correlates with Transcriptomics in the Alzheimer’s Disease Continuum

Bridging the gap between cortical morphometric remodeling and gene expression can help 1 to clarify the effects of the selective brain accumulation of Amyloid-β (Aβ) and tau proteins occurring 2 in the Alzheimer’s Disease (AD). To this aim, we derived morphometric similarity (MS) networks from 3 126 Aβ and tau positive (Aβ+/tau+) and 172 Aβ-/tau- subjects, and we investigated the association 4 between group-wise regional MS differences and transcriptional correlates thanks to an imaging 5 transcriptomics approach grounding on the Allen Human Brain Atlas (AHBA). The expressed gene 6 with the highest correlation with MS alterations was BCHE, a gene related to Aβ homeostasis. In 7 addition, notably, among the most promising results derived from the enrichment analysis, we found 8 the immune response as biological process, and astrocytes, microglia, and oligodendrocyte precursors 9 for the cell types. In summary, by relating cortical MS and AHBA-derived transcriptomics, we were 10 able to retrieve findings suggesting the biological mechanisms underlying the Aβ and tau-induced 11 cortical MS alterations in the AD continuum.