From Alzheimer’s Disease to Rare Diseases: Exploring the Gut–Brain Axis in Neurodegeneration

Neurodegenerative diseases, among the leading causes of death worldwide, are characterized by progressive neuronal loss and limited therapeutic options. Growing evidence points to shared mechanisms, including glial dysfunction, metabolic alterations, and immune imbalances. This project will compare Alzheimer’s disease (AD), the most common form, with autosomal dominant leukodystrophy (ADLD), a rare demyelinating disorder associated with the LMNB1 gene. Biological fluids and the microbiota of patients and healthy controls will be analyzed, focusing on the gut–brain axis, to identify shared systemic signatures. Both 2D and 3D hiPSC-derived models, including brain organoids, neurons, astrocytes, and oligodendrocytes, will help clarify the underlying molecular mechanisms. The aim is to identify new biomarkers and shared biological pathways, supporting innovative diagnostic and therapeutic approaches.