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Proposed minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life

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Abstract

Aim

The aim of this study was to identify the minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life.

Methods

We searched the Online Mendelian Inheritance in Man (OMIM) database to extract the validated human genes annotated (until March 2020) for five major disorders of pathophysiological overlap and sequential chronological occurrence in human, including multiple sclerosis, type 2 diabetes mellitus, Alzheimer’s disease, vascular dementia, and Lewy body dementia. Gene co-expression and physical interaction networks were subsequently constructed for the overlapping genes across the selected disorders.

Results

Remarkably, each of the gene co-expression and physical interaction networks consisted of single clusters (P = 0.0005 and P = 1 × 10−16, respectively). APP was the major hub in the integrated and tissue-specific co-expression networks, whereas insulin was the major hub in the physical interaction network. Several other hubs were identified across the identified networks, including TNF, VEGFA, GAPDH, and NOTCH1.

Conclusion

We propose the minimal co-expression and physical interaction networks and their single clustering in the development of cognition impairment in human mid and late life. This is a pilot study, warranting identification of more risk genes, using additional validated databases in the future.

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Abbreviations

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

CNS:

Central nervous system

GDPH:

Glyceraldehyde-3-phosphate dehydrogenase

GO:

Gene ontology

GSEA:

Gene set enrichment analysis

IGFR:

Insulin-like growth factor receptor

IL1RN:

Interleukin 1 receptor antagonist

INS:

Insulin

INSR:

Insulin receptor

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LBD:

Lewy body dementia

MS:

Multiple sclerosis

NCD:

Neurocognitive disorder

OMIM:

Online Mendelian Inheritance in Man

T2DM:

Type 2 diabetes mellitus

TNF:

Tumor necrosis factor

VD:

Vascular dementia

VEGFA:

Vascular endothelial growth factor alpha

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Correspondence to Mina Ohadi.

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Salehi, Z., Arabfard, M., Sadatpour, O. et al. Proposed minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life. Neurol Sci 42, 951–959 (2021). https://doi.org/10.1007/s10072-020-04594-0

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