Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that causes cognitive impairment for which neither treatable nor preventable approaches have been confirmed. Although genetic factors are considered to contribute to sporadic AD, for the majority of AD patients, the exact causes of AD aren’t fully understood. For AD genetics, we developed cellular dissection of polygenicity (CDiP) technology to identify the smallest unit of AD, i.e., genetic factors at a cellular level. By CDiP, we found potential therapeutic targets, a rare variant for disease stratification, and polygenes to predict real-world AD by using the real-world data of AD cohort studies (Alzheimer’s Disease Neuroimaging Initiative: ADNI and Japanese Alzheimer’s Disease Neuroimaging Initiative: J-ADNI). In this review, we describe the components and results of CDiP in AD, induced pluripotent stem cell (iPSC) cohort, a cell genome-wide association study (cell GWAS), and machine learning. And finally, we discuss the future perspectives of CDiP technology for reverse engineering of sporadic AD toward AD eradication.