Abstract
Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from AD patients have proven to be a reliable model for AD pathogenesis. Here, we have conducted an in silico analysis aimed at identifying pathogenic gene-expression profiles and novel drug candidates. The GSE117589 microarray dataset was used for the identification of Differentially Expressed Genes (DEGs) between iPSC-derived neuronal progenitor (NP) cells and neurons from AD patients and healthy donors. The Discriminant Analysis Module (DAM) algorithm was used for the identification of biomarkers of disease. Drugs with anti-signature gene perturbation profiles were identified using the L1000FWD software. DAM analysis was used to identify a list of potential biomarkers among the DEGs, able to discriminate AD patients from healthy people. Finally, anti-signature perturbation analysis identified potential anti-AD drugs. This study set the basis for the investigation of potential novel pharmacological strategies for AD. Furthermore, a subset of genes for the early diagnosis of AD is proposed.
Highlights
Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide
Magnetic resonance imaging (MRI)-based regional brain volumes, cerebrospinal fluid (CSF) analytes, and positron emission tomography (PET) imaging of cerebral fibrillar β-amyloid along ad hoc cognitive tests have been investigated as biomarkers of disease, they are useful only for the late stages of the disease, and may not be sensitive enough to detect initial neuropathophysiological processes occurring in AD patients who show mild cognitive impairment [2,3]
Gene Ontology analysis revealed a partial overlapping of enriched biological processes among the upregulated Differentially Expressed Genes (DEGs) in AD neuronal progenitors (NP) cells and neurons, that included “regulation of ion transport”, “regulation of neuron differentiation”, “chemical synaptic transmission”, “neuron projection morphogenesis”, “negative regulation of cell differentiation” and “axon guidance” (Figure 2A,B)
Summary
Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. The disease shows a prodromal period that can last for decades and is characterized by a preclinical asymptomatic phase before cognitive. Brain Sci. 2020, 10, 166 impairment occurs [1]. Mild cognitive impairment (MCI) represents the first clinical phase of AD, characterized by an alteration in episodic memory. Magnetic resonance imaging (MRI)-based regional brain volumes, cerebrospinal fluid (CSF) analytes, and positron emission tomography (PET) imaging of cerebral fibrillar β-amyloid along ad hoc cognitive tests have been investigated as biomarkers of disease, they are useful only for the late stages of the disease, and may not be sensitive enough to detect initial neuropathophysiological processes occurring in AD patients who show mild cognitive impairment [2,3]
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