This is a 24-month, monocentric, exploratory and observational clinical study aimed at developing and validating a blood-based diagnostic test for Alzheimer's disease (AD). The test is based on two complementary biomarkers: conformational changes in Protein Kinase C (PKC) and aggregation of β-amyloid peptide on red blood cell membranes. The study will also establish a biobank of serum, plasma, urine, and RNA samples for future biomarker research.

Inclusion Criteria:

For All Participants (HV and AD groups):

• Age between 50 and 85 years
• Ability to understand and sign informed consent
• Availability for the full duration of the study (24 months)
• Fasting capability for morning sample collection (between 8:30-12:00)
• Willingness to provide blood and urine samples for biomarker analysis and biobank storage

Additional Criteria for Healthy Volunteers (HV):

• No history or current diagnosis of neurodegenerative disease
• Normal cognitive function confirmed by neuropsychological testing (e.g., MMSE score within normal range)
• No significant abnormalities on brain imaging (CT or MRI if performed)
• No use of medications affecting cognitive function

Additional Criteria for Alzheimer's Disease Patients (AD):

• Clinical diagnosis of probable Alzheimer's disease based on standardized criteria
• Cognitive impairment confirmed by neuropsychological testing (e.g., MMSE score below threshold)
• Supporting evidence from brain imaging (CT or MRI) and/or cerebrospinal fluid biomarkers (if available)
• Stable medical condition allowing participation in study procedures

Exclusion Criteria:

For All Participants:

• History of major psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• Significant neurological conditions other than Alzheimer's disease (e.g., Parkinson's disease, stroke)
• Active malignancy or history of cancer within the past 5 years (except localized skin cancer)
• Severe renal, hepatic, or cardiovascular disease
• Current participation in another interventional clinical trial
• Known blood disorders or conditions affecting red blood cell morphology or function
• Recent blood transfusion (within 3 months)
• Substance abuse or alcohol dependence
• Inability to comply with study procedures

Additional Exclusion for Healthy Volunteers:

• Any cognitive complaints or subjective memory loss
• First-degree family history of Alzheimer's disease (optional, depending on stratification strategy)
• Use of psychoactive medications

Additional Exclusion for Alzheimer's Disease Patients:

• Diagnosis of mixed or atypical dementia
• Rapidly progressive cognitive decline suggestive of other pathology
• Contraindications to lumbar puncture (if CSF sampling is planned)

The study population consists of 200 individuals aged 50 to 85 years, divided into two cohorts:

Healthy Volunteers (HV): 100 cognitively healthy individuals with no history of neurodegenerative disease. These participants will serve as controls for biomarker comparison.

Alzheimer's Disease Patients (AD): 100 individuals clinically diagnosed with probable Alzheimer's disease based on neuropsychological testing, clinical evaluation, and imaging. These participants represent the target population for biomarker validation.

Participants will be stratified by age and sex to ensure balanced representation across both groups. All subjects must be able to provide informed consent and comply with study procedures, including fasting sample collection and clinical assessments.