A study co-ordinated by the University of Insubria, in collaboration with the Universities of Milano-Bicocca, Statale di Milano and Tor Vergata, has shown that Alzheimer's alters the interaction between proteins and cell physiology differently between men and women. A woman suffering from Alzheimer's disease, therefore, has a different metabolic profile from a man with the same disease because the disease activates or does not activate different physiopathological mechanisms depending on gender. The results of the study open up the possibility of innovative therapeutic approaches differentiating between men and women.
In order to clarify the alterations linked to ageing versus those linked to pathology, a molecular study (so-called 'omics' because it is based on transcriptomic, proteomic and metabolomic analyses, including chiral analyses) was carried out by a research team composed of Professor Gabriella Tedeschi of the University of Milan, Professor Loredano Pollegioni, head of The Protein Factory 2. 0 laboratory of the University of Insubria, Professor Paola Coccetti of the University of Milano-Bicocca (Dr. Farida Tripodi in the research group) and Dr Nadia Canu, professor at the University of Rome Tor Vergata, under the supervision of Professor Loredano Pollegioni.
The work, published in the journal Cell Reports, analysed post mortem samples of the hypothalamus from brains of men and women with normal ageing and from patients suffering from Alzheimer's disease. Profound differences are revealed in terms of altered metabolic pathways between healthy controls and the male and female patient cohorts. In particular, a decreased insulin response is evident in Alzheimer's syndrome comparing females with males. In addition, the serine metabolism (which generates an important neuromodulator, D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men whereas in women this value is only modified during the onset of Alzheimer's disease. These results show how Alzheimer’s disease changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women.