Brain estrogen receptor expression in the perimenopausal transition: kinetic and geometric analyses of [18F]-fluoroestradiol (FES) PET/CT and correlation with neuropsychological, biochemical and magnetic resonance imaging biomarkers.
Mid-life disturbances of metabolic and hormonal factors have been hypothesized contribute to the observed higher Alzheimer’s disease (AD) prevalence among women. Perimenopausal and postmenopausal women have been shown to exhibit neuronal volume loss (including hippocampal volume), relative hypometabolism, and slightly but measurable higher rates of AD-endophenotype biomarkers-based progression compared to premenopausal women.
Fluorine-18 16a-fluoroestradiol (FES) is a ligand for the estrogen receptor (ER) that has been used to image estrogen-receptor-rich tumours in humans. Few studies based on either the equilibrium or FES kinetic analysis have suggested the potential usefulness of FES-PET to the study of cerebral ER expression in high receptor density regions such as the pituitary and hypothalamus.
In recent years, data in rats highlighted the highest levels of uptake of 18F-FES in the pituitary, hypothalamus, bed nucleus of the stria terminalis, and amygdala. This multimodal brain imaging project aims to investigate ER expression in the brain, in vivo through FES-PET, in cognitively intact females during the perimenopausal transition. We aim to quantify FES-PET signal in high ER density regions as well as to develop new data-driven methods to improve FES-PET signal detection in regions with relatively lower ER expression such as the hippocampus. Using FES-PET, we will quantify brain ER in 60 cognitively intact females (age range 40-60 years recruited based on their hormonal status as 20 premenopausal, 20 perimenopausal, 20 postmenopausal women). Assessment of brain ER expression will be based on multiple-time graphical analyses and innovative post-processing analyses for semi-quantification of FES-PET signal developed ad hoc for the present project following a data-driven pipeline already used by our group to analyze PET data acquired with other experimental tracers. Our secondary aims will be the exploration of the interplay between FES-PET functional extracted measures of brain ER expression, hormonal status (chronological versus hormonal age), clinical/demographic variables, cognitive scales, large-scale network connectivity metrics measured by resting-state functional MRI (rs-fMRI) and morphological/geometrical MRI-based data in the whole brain and AD-vulnerable regions.
The possibility to measure brain ER expression might further highlight the relevance of estrogen in cognition, brain bioenergetics and risk for AD in women. Moreover, the possibility to quantify ER over time and to assess the correlation between ER expression and clinical-biochemical markers might open to treatment approaches with specific drugs or other types of interventions targeting this pathway.
Data di avvio 18 Ottobre 2023
Data di completamento 18 Ottobre 2025
Total cost € 90874,00
Progetto 2022WK7NHC finanziato all’interno del Bando PRIN 2022 di cui al Decreto Direttoriale n. 104 del 02/02/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23019060006
Ultimo aggiornamento
31.05.2024