Motivatedby the great need to develop biomarkers for early diagnosisof neurodegenerative diseases and by the outstanding possibilitiesoffered by the rapid development of in silico hard- and software,in this work, we have carried out a computational investigation offirst- and second-generation PET tracers for 4R tau fibrils basedon fundamental atomic principles. This evidence concerns the gene MAPT and neurodegenerative disease.