Transcriptome analysis reveals potential marker genes for diagnosis of Alzheimer’s disease and vascular dementia

Abstract

Alzheimer’s disease (AD) and vascular dementia (VD) are the two most common forms of dementia, share similar symptoms, and are sometimes difficult to distinguish. To investigate the potential mechanisms by which they differ, we identified differentially expressed genes in blood and brain samples from patients with these diseases, and performed weighted gene co-expression network analysis and other bioinformatics analyses. Weighted gene co-expression network analysis resulted in mining of different modules based on differences in gene expression between these two diseases. Enrichment analysis and generation of a protein-protein interaction network were used to identify core pathways for each disease. Modules were significantly involved in cAMP and AMPK signaling pathway, which may be regulated cell death in AD and VD. Genes of cAMP and neurotrophin signaling pathways, including ATP1A3, PP2A, NCEH1, ITPR1, CAMKK2, and HDAC1, were identified as key markers. Using the least absolute shrinkage and selection operator method, a diagnostic model for AD and VD was generated and verified through analysis of gene expression in blood of patients. Furthermore, single sample gene set enrichment analysis was used to characterize immune cell infiltration into brain tissue. That results showed that infiltration of DCs and pDCs cells was increased, and infiltration of B cells and TFH cells was decreased in the brain tissues of patients with AD and VD. In summary, classification based on target genes showed good diagnostic efficiency, and filled the gap in the diagnostic field or optimizes the existing diagnostic model, which could be used to distinguish between AD and VD.

Mapping the spatial proteomic signature of dorsal and ventral hippocampus in a mouse model of early Alzheimer’s disease: changes in synaptic plasticity-related proteins associated with sexual dimorphism

“…Another altered protein related to LTP maintenance is CaMKK2. This kinase is necessary for late-LTP, since it is involved in the synthesis of plasticity related proteins and the subsequent memory consolidation (Figure 6) [79–83], and the overactivation of this pathway has been related to synaptic loss in a transgenic AD mice model [84, 85]. Interestingly, CaMKK2 has a male-specific role in hippocampal memory formation [86], thus the overexpression of CaMKK2 in male mice after oA β 1-42 injection might be contributing to LTP and memory deficits specifically in males.…”

“…Another altered protein related to LTP maintenance is CaMKK2. This kinase is necessary for late-LTP, since it is involved in the synthesis of plasticity related proteins and the subsequent memory consolidation (Figure 6) [79][80][81][82][83], and the overactivation of this pathway has been related to synaptic loss in a transgenic AD mice model [84,85].…”

In Silico Analysis Reveals the Modulation of Ion Transmembrane Transporters in the Cerebellum of Alzheimer’s Disease Patients

“…P-type ATPases are essential ion-transporting pumps while V-type ATPase acidify different intracellular organelles and pump protons across the plasma membranes. ATP1A3 was previously identified as one potential marker for AD diagnosis compared with vascular dementia [ 40 ]. It encodes for Na + /K + -ATPase α3 subunit (NAKα3).…”

Classification Prediction of Alzheimer’s Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images

“…In comparing AD and VaD, one study has demonstrated differential patterns of CBF reduction in the frontal and parietal cortices [16], while another study has indicated reductions in the frontal and temporal regions [17]. Furthermore, recent years have seen a growing number of studies leveraging biological data, such as biomarkers and marker genes, to delve into the distinctions between AD and VaD [18][19][20]. This approach aids in enhancing our comprehension of disease pathways and mechanisms, and serves to validate prevailing hypotheses.…”