Potential Molecular Mechanisms of Alzheimer's Disease from Genetic Studies

Simple Summary We systematically reviewed genetic studies employing single-cell transcriptomics (scRNA-seq) or spatial genomics in Alzheimer's disease (AD) research to highlight potential molecular mechanisms and explore what changed from previous findings. An overview of molecular imbalances in AD and differences in their mechanisms across sex, period of onset, age, and immunity are presented. Our study provides evidence for continuing research to identify common causes and possible solutions to ameliorate AD. scRNA-seq and spatial transcriptomics have the advantage of providing more in-depth results, which is vital for identifying crucial factors for AD-modifying investigations. The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that affects cognition, and molecular imbalance is one of its hallmarks. There is a need to identify common causes of molecular imbalance in AD and their potential mechanisms for continuing research. A narrative synthesis of molecular mechanisms in AD from primary studies that employed single-cell sequencing (scRNA-seq) or spatial genomics was conducted using Embase and PubMed databases. We found that differences in molecular mechanisms in AD could be grouped into four key categories: sex-specific features, early-onset features, aging, and immune system pathways. The reported causes of molecular imbalance were alterations in bile acid (BA) synthesis, PITRM1, TREM2, olfactory mucosa (OM) cells, cholesterol catabolism, NFkB, double-strand break (DSB) neuronal damage, P65KD silencing, tau and APOE expression. What changed from previous findings in contrast to results obtained were explored to find potential factors for AD-modifying investigations.