CoED5013 Innate Memory-related blood Biomarkers as a proxy of microglia-mediated neurodegeneration to predict early AD progression (ADIMB)

Alzheimer's disease (AD) is a severe and progressive illness of the brain. It is characterized by neuronal death and consequent impairment of memory, thinking and behavior. So far AD is incurable mainly because its diagnosis is based on symptoms developed because of the irreversible neuronal damage, thus too late for efficacious intervention. Recent studies suggest that inflammation in the brain, influenced by peripheral inflammatory conditions, is a main driver of this disease. The present research project will focus on patients with early AD and is addressed to evaluate changes in blood immune cells that are related to brain inflammation, early neuronal damage and severity of early symptoms. Our goal is to identify efficient blood tests to help diagnose AD and evaluate treatments. This result will be useful in making clinical trials more rigorous and affordable, will accelerate drug development and will improve clinical care by providing access to accurate diagnoses.

Inflammation is a driving force in Alzheimer's disease (AD) and besides brain resident microglia, other innate immune cells from periphery, including dendritic cells (DCs), may have a role in AD pathogenesis and progression. Recent evidence indicates that following exposition to various stimuli, host innate immune cells undergo a mechanism of inflammation enhancement named innate memory (IM), which could contribute to neurodegeneration. DCs, a unique type of migratory innate immune cells that induce and regulate immune responses and inflammation, are subjected to IM reprogramming and orchestrate brain immune surveillance. In AD patients, DCs are dysfunctional and show pro-inflammatory profiles, thus when recruited to brain could contribute to neuropathology and promote neurodegeneration, reflecting the progression of disease. Aim of this project is to study AD patients at early disease stages in order to assess their blood levels of DCs as an index of cell recruitment to brain and define the IM status of their DCs in terms of enhanced inflammatory cytokine recall responses and epigenetic modifications following in vitro stimulations. The identified peripheral immune changes will be related to microglial activation, amyloid load and symptomatology to identify new peripheral biomarkers potentially helpful for diagnosis and disease progression tracking.

Inflammation is a driving force in Alzheimer's disease (AD) and besides brain resident microglia, other innate immune cells from periphery, including dendritic cells (DCs), may have a role in AD pathogenesis and progression. Recent evidence indicates that following exposition to various stimuli, host innate immune cells undergo a mechanism of inflammation enhancement named innate memory (IM), which could contribute to neurodegeneration. DCs, a unique type of migratory innate immune cells that induce and regulate immune responses and inflammation, are subjected to IM reprogramming and orchestrate brain immune surveillance. In AD patients, DCs are dysfunctional and show pro-inflammatory profiles, thus when recruited to brain could contribute to neuropathology and promote neurodegeneration, reflecting the progression of disease. Aim of this project is to study AD patients at early disease stages in order to assess their blood levels of DCs as an index of cell recruitment to brain and define the IM status of their DCs in terms of enhanced inflammatory cytokine recall responses and epigenetic modifications following in vitro stimulations. The identified peripheral immune changes will be related to microglial activation, amyloid load and symptomatology to identify new peripheral biomarkers potentially helpful for diagnosis and disease progression tracking.