Title:Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease
Volume: 22
Issue: 6
Author(s): Kevins Jara-Medina, Luis Lillo, Constanza Lagunas, Gerardo Cabello-Guzmán and Francisco J. Valenzuela-Melgarejo*
Affiliation:
- Department of Basic Sciences, Universidad del Bío-Bío, Campus Fernando May, Chillán, Chile. Andrés Bello 720,
Casilla 447 - CP - 3800708
Keywords:
Alzheimer, vascular, dementia, bioinformatics, genes, DEG.
Abstract:
Background: Alzheimer's disease (AD) plays a prominent role as the most common
form of dementia. Moreover, the traditional mechanism of AD does not explain the microvascular
damage observed in about 25-30 years between the onset of AD, which results in late application
treatment that inhibits or delays neurodegeneration.
Objective: Our objective was to identify differentially expressed genes in human brain samples associated
with vascular disruption in AD.
Methods: We analyzed 1633 post-mortem brain samples in the GEO database and, after applying
clinical and bioinformatic exclusion criteria, worked with 581 prefrontal and frontal samples. All
datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny
tool, and their metabolic relevance associated with AD and the vascular system was analyzed using
MetaboAnalyst tools.
Results: Our bioinformatic analysis identified PRKCB, MAP2K2, ADCY1, GNA11, GNAQ,
PRKACB, KCNMB4, CALD1, and GNAS as potentially involved in AD pathogenesis. These
genes are associated with signal transductions, cell death signaling, and cytoskeleton, suggesting
potential modulation of cellular physiology, including endoplasmic reticulum and mitochondrial
activity.
Conclusion: This study generates hypotheses regarding the roles of novel genes over critical pathways
relevant to AD and its relation with vascular dysfunction. These findings suggest potential
new targets for further investigation into the pathogenesis of dementia and AD.