1. Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus
- Author
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Elisa Maffioli, Giulia Murtas, Valentina Rabattoni, Beatrice Badone, Farida Tripodi, Filomena Iannuzzi, Danilo Licastro, Simona Nonnis, Anna Maria Rinaldi, Zoraide Motta, Silvia Sacchi, Nadia Canu, Gabriella Tedeschi, Paola Coccetti, Loredano Pollegioni, Maffioli, E, Murtas, G, Rabattoni, V, Badone, B, Tripodi, F, Iannuzzi, F, Licastro, D, Nonnis, S, Rinaldi, A, Motta, Z, Sacchi, S, Canu, N, Tedeschi, G, Coccetti, P, and Pollegioni, L
- Subjects
Proteomics ,Male ,sex differences ,insulin ,sex difference ,D-serine ,amino acid metabolism ,Receptors, N-Methyl-D-Aspartate ,Hippocampus ,General Biochemistry, Genetics and Molecular Biology ,transcriptomics ,Alzheimer Disease ,Settore BIO/10 - Biochimica ,Receptors ,Serine ,Humans ,phosphorylated pathway ,proteomic ,aging ,transcriptomic ,NMDA receptor ,BIO/10 - BIOCHIMICA ,CP: Metabolism ,CP: Neuroscience ,metabolomics ,proteomics ,Female ,Insulin ,Quality of Life ,metabolomic ,N-Methyl-D-Aspartate - Abstract
Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women.
- Published
- 2022