Hippocampal Proteomics Profiling Along with Protein-Protein Interaction Analysis Elucidates Alzheimer's Disease Pathways and Genes

Alzheimer's disease (AD), a neuro-degenerative disorder is posing threat to the ever increasing elderly people of the world. Identification of the key protein expression and understanding the dynamics of the molecular networks accompanying the progression of AD may help in the development AD biomarkers. Thus the preset study had been aimed at comparing the control and AD model rats' hippocampal proteomics followed by deciphering the protein-protein interaction (PPI) and the ingenuity pathway analyses (IPA). A total of 822 proteins were identified with minimum peptide 2, threshold 95.0% and peptide threshold at 0.1% FDR. Among them, 329 were differentially expressed (P<0.05) and 289 had log fold change of 1.5 and above (chapter 7, section 7.4). Number of proteins linked with AD was 59. Most of the down-regulated proteins in the AD rats were involved in neurotransmission, synaptic functions, stress response, mitochondrial oxidative phosphorylation and neuronal cytoskeleton maintenance. PPI analyses of the significantly expressed proteins with log fold change value of 1.5 and above were showed different interacting networks among the proteins. IPA analyses of the same proteins revealed the connectivity strength among different networks and identified the functional pathway interactions among them. The top-most network has been associated with cell death and survival, neurological diseases and psychological disorders. The second top-most network involved physiological system development and functions included molecular transport, cell-cell signaling and interaction, nervous system development and functions. Current findings pave a new vista towards understanding of AD progression and development of therapeutic strategy against AD. Funding: The authors gratefully thank University of Malaya and the Ministry of Higher Education, Malaysia for the HIR-MOHE Research Grant 02-21001 funding and Mohammad Azizur Rahman is grateful for the grant-in-aid provided by Jahangirnagar University and the University Grants Commission of Bangladesh. Declaration of Interest: The authors declare no competing interests. Ethical Approval: All the experimental protocols had been approved by the ethical permission committee, University of Malaya Institutional Animal Care and Use Committee (UMIACUC) [Ethics reference no. ISB/25/04/2013/NA (R)].