In-depth Analysis of Cholesterol Metabolism and Related Biomarkers in the Pathogenesis and Progression of the Disease in Neurodegenerative Dementias

The aim of the study is to evaluate the role of cholesterol in the pathogenesis of neurodegenerative dementias. Hypercholesterolemia is a known risk factor for Alzheimer disease (AD), and oxysterols, the principal cholesterol metabolites, are involved in neuroinflammation, amyloid aggregation, and tau accumulation. Oxysterols will be measured in different biological samples (post-mortem brain tissue, CSF, and plasma) from patients with different neurodegenerative dementias, including AD, frontotemporal dementia (FTD), and primary tauopathies. This approach will allow determination of whether their modifications correlate primarily with Aß deposition, tauopathy, or neuronal loss, with the goal of identifying correlations with disease severity and progression. Since preliminary results suggest that the levels of most oxysterols in the brain significantly increase in parallel with the levels of the enzyme PCSK9, the investigators will explore the role of cholesterol metabolism and PCSK9 in AD and other dementias to evaluate whether cholesterol dysregulation represents a common alteration across these neurodegenerative disorders or is specific to AD

Inclusion Criteria: * Age 40-85 * Diagnosis based on the current diagnostic criteria for AD (McKhann et al., 2011), FTD (Gorno-Tempini et al., 2011; Rascovsky et al., 2011), PSP and CBD (Amstrong et al., 2013; Höglinger et al., 2017) * Mini Mental State Examination MMSE \> 10. Exclusion Criteria: * Other neurological or psychiatric disorders Severe chronic metabolic diseases