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 mecha-nisms are active in men and women.

Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus / E. Maffioli, G. Murtas, V. Rabattoni, B. Badone, F. Tripodi, F. Iannuzzi, D. Licastro, S. Nonnis, A.M. Rinaldi, Z. Motta, S. Sacchi, N. Canu, G. Tedeschi, P. Coccetti, L. Pollegioni. - In: CELL REPORTS. - ISSN 2211-1247. - 40:10(2022 Sep 06), pp. 111271.1-111271.25. [10.1016/j.celrep.2022.111271]

Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus

E. Maffioli
Primo
;
S. Nonnis;G. Tedeschi
;
2022

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 mecha-nisms are active in men and women.
CP: Metabolism; CP: Neuroscience; D-serine; NMDA receptor; aging; amino acid metabolism; insulin; metabolomics; phosphorylated pathway; proteomics; sex differences; transcriptomics; Female; Hippocampus; Humans; Insulin; Male; Proteomics; Quality of Life; Receptors, N-Methyl-D-Aspartate; Serine; Alzheimer Disease
Settore BIO/10 - Biochimica
PRIN201719GTEDE_01 - Dissecting serine metabolism in the brain - TEDESCHI, GABRIELLA - PRIN2017 - PRIN bando 2017 - 2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/944814
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