Computational Molecular Biology 2025, Vol.15, No.5, 254-264 http://bioscipublisher.com/index.php/cmb 255 focuses not only on which molecular drivers or cell-level interactions they reveal, but also on how they help explain the changes in brain networks during disease progression. At the same time, the value of these results in screening potential biomarkers and therapeutic targets was also discussed, hoping to provide some references for promoting precision medicine research in the field of AD. 2 Molecular Basis of Alzheimer's Disease Many molecular changes in Alzheimer's disease (AD) often start to accumulate before symptoms appear, but people usually become aware of their existence only when cognitive decline or memory problems arise. Aβ plaques and hyperphosphorylated tau protein tangles are still regarded as major markers, as they disrupt communication between neurons, but these are not all. Mitochondrial damage, increased oxidative stress and persistent neuroinflammation are also involved, resulting in a "multi-point imbalance" state at the molecular level of AD (Guo et al., 2020). In recent years, multi-omics studies have continuously expanded this picture. Multiple pathways, including neurotransmitter signaling, the immune system, lipid metabolism, and even cell transport, have all shown varying degrees of disorder, indicating that the progression of AD is not a single route but the result of multiple pathways simultaneously deviating from the normal track. 2.1 Genetic contributors to AD At the genetic level, the risk of AD is not exactly the same. Some familial cases are caused by mutations in APP, PSEN1 or PSEN2, which lead to deviations in amyloid protein processing. Such patients often develop the disease at an earlier age. However, more people encounter late-onset AD (LOAD), with more scattered and complex influencing factors, among which APOE ε4 is the most prominent one. More than forty risk loci have been identified by GWAS, but the directions they involve are not entirely consistent. Immunity, lipid metabolism, and endocytosis are all related. Rare variations such as TREM2, SORL1, and ABCA7 mostly affect microglia and innate immune function. However, the specific effects of many variations remain unclear and require combined analysis of genetics and transcriptomics to be further clarified (Gao et al., 2025; Han et al., 2025). That is to say, although genetic factors are important, their influence is not linear. Instead, they may present different disease course trajectories due to different individual gene combinations. 2.2 Transcriptomic and proteomic dysregulation When the focus is extended from the genetic level to the transcriptional and protein levels, it can be seen that the changes that occur in the brain tissue of AD are more diverse. Transcriptome studies have shown that not only immune-related genes change, but also the expression patterns related to synaptic activity and metabolism deviate from normal. With the development of RNA sequencing and single-cell analysis methods, an increasing number of cell type-specific expression changes have been identified, including the contribution of certain alternative splicing events in the disease process. The information provided by proteomics is more intuitive: the protein networks involved in inflammatory responses, complement activation and mitochondrial function are often in an abnormal state, accompanied by some changes in post-translational modifications. Combining these data can more clearly outline the key molecular characteristics related to amyloid deposition and neurodegeneration, and also provide more clues for finding potential biomarkers and therapeutic targets (Figure 1) (Bai et al., 2020; Tijms et al., 2024). 2.3 Cellular and pathway-level dysfunctions When discussing Alzheimer's disease (AD), the changes at the cellular level are often not caused by a single source. Different types of cells, such as neurons, microglia, astrocytes, and even brain endothelial cells, all have their own ways of being affected. For instance, neurons are more likely to exhibit synaptic reduction, and the phenomenon of enhanced inflammation is usually closely related to the activity of microglia. When the blood-brain barrier becomes fragile, external factors are also more likely to interfere with the internal brain environment, making the problem more complicated. However, these changes do not only occur separately in different cells. Multi-omics studies have shown that pathways such as immune response, oxidative stress, calcium signaling, and cell adhesion molecules are often simultaneously "activated". In addition, with mitochondrial dynamics disorders and weakened autophagy processes, it is naturally more difficult for neurons to maintain
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