Potential Molecular Mechanisms of Alzheimer's Disease from Genetic Studies

Biology (Basel). 2023 Apr 15;12(4):602. doi: 10.3390/biology12040602.

Abstract

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.

Keywords: Alzheimer’s disease; molecular mechanisms; single-cell transcriptomics; spatial genomics.

Publication types

  • Systematic Review