The present single center clinical chronobiological study on 24 subjects (12 patients with mild to moderate form of Alzheimer's disease and 12 Healthy subjects) aims at characterizing the ADDIA biomarkers: a) blood cell-based biomarkers measured by flow cytometry using proprietary probes specific of two targeted biomarkers, beta-Amyloid (Aβ) peptide and a kinase, and b) circulating biomarkers in peripheral body fluids. The biomarkers will be analyzed on samples taken at different time points of the day, including under fasting and non-fasting conditions and at two periods: day 1 and day 14.

Inclusion Criteria for Alzheimer patient group:

• Signed Informed Consent.

• Male or female subject, between 55 and 85 years inclusive.

• Specific clinical phenotype of AD: Presence of an early and significant episodic memory impairment (isolated or associated with other cognitive or behavioural changes that are suggestive of a dementia syndrome) that includes the following:

  • Gradual and progressive change in memory function reported by patient or informant over more than 6 months.
  • Objective evidence of an amnesic syndrome of hippocampal type, based on significantly impaired performance on an episodic memory test with established specificity for mild to moderate AD.

• Cognitive tests including MMSE score 12 ≤ MMSE ≤ 25 for mild to moderate AD (measured in the last 3 months), b) Scores of other tests routinely practiced at the hospital for measurement of memory and cognition shall be compatible with mild to moderate AD.

• Neuroimaging compatible with a diagnosis of mild to moderate AD.

• Cerebrospinal fluid (CSF) biomarkers showing at least 2 positive levels out of the 3 biomarkers: CSF Aβ1-42 and tau (Phosphorylated-Tau and/or Total-Tau). CSF collection and data being only retrospective.

Inclusion Criteria for healthy controls:

• Signed Informed Consent.
• Male or female subject, between 55 and 85 years inclusive.
• Normal clinical and cognitive scores as measured using standard neuropsychological tests.
• Normal scores in other neuropsychological tests routinely practiced at the hospital for measurement of memory and cognition.
• No abnormal neuroimaging findings in at least structural MRI.

Exclusion Criteria:

• Any subject who did not sign the informed consent form.
• Any chronic neurodegenerative disease (vascular dementia, Parkinson's disease, Creutzfeldt Jacob, Huntington's disease, etc.), acute neurodegenerative disease (stroke), history or presence of clinically relevant psychiatric history (schizophrenia, psychosis), some chronic inflammatory diseases that impact blood cells (e.g. anemia of inflammation and chronic disease) and some cancers (that impact blood cells: e.g. leukemia), major sensory deficits that could interfere with cognitive assessment (visual and auditory), epilepsy.
• Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Blood donation, any volume, within 2 months before inclusion.
• Neutropenia (Neutrophils < 1500/mm3).
• Thrombocytopenia (platelets: < 100,000/mm3, rule out EDTA-induced pseudothrombocytopenia).

• 12 patients with mild to moderate form of Alzheimer's disease 55 to 85 years-old.
• 12 healthy volunteers (HV), 55 to 85 years-old.
• Total expected completed subjects: 24.
• Stratification by gender: 6 males and 6 females, age-matched healthy subjects and 6 males and 6 females, age-matched Alzheimer patients.
• Mean age similar in both groups