ABSTRACT: A gene expression profile has not been identified for late-onset Alzheimer's Disease (LOAD) in more than 95% of cases. However, autosomal dominant genes are known for their early-onset (EOAD) characteristics. Moreover, the genetic convergences between familial EOAD and sporadic LOAD have not previously been identified despite the common neuropathology. Here, synchronized skin fibroblast samples from individuals with LOAD, confirmed by autopsy, revealed 36 statistically significant (P<0.05) LOAD-dysregulated genes, with 26 showing an essential gap with non-Alzheimer's disease (non-ADD) dementia patients. Notably, five LOAD-dysregulated genes in the skin—FAM149B, NHLH1, SHISA5, URB2, and WASF2—were also dysregulated in blood B-lymphocytes. Importantly, an additional 18 LOAD-dysregulated gene families in the skin were validated in the blood. In total, 23 LOAD-dysregulated gene families in the skin were confirmed in the blood. An intriguing and novel aspect is the genetic convergence between late-onset and early-onset Alzheimer's disease, as demonstrated by dysregulated gene families, including ADAM, IL, and RAB. The gene expression profile aligns remarkably well with prior autopsy-validated biomarkers: Morphometric Imaging, PKC epsilon, Cell Size, Growth Rate, and Protein Amount. Our findings suggest a promising potential for personalized genomic profiling in the diagnosis and treatment of LOAD, offering hope for more effective and targeted approaches.
