Alzheimer's disease (AD) is the most common neurodegenerative disease. Age is its main risk factor. AD is a multifactorial disease, combining genetic and environmental risk factors. Autosomal dominant mutations have been identified (PSEN1, PSEN2, APP), leading to earlier and more severe forms of the disease. Other genetic risk factors have been identified, such as the ε4 allele of the APOE gene. . The environment also plays a major role, with the identification of several risk factors such as air pollution or nutritional deficiencies.

AD patients frequently present hyperhomocysteinemia, a consequence of a dysfunction of monocarbon metabolism. Homocysteine is an amino acid involved in the metabolism of methionine and cysteine. High concentrations of homocysteine can be deleterious to the central nervous system.

Most prospective studies have shown that elevated homocysteine is a predictor of undefined cognitive impairment or AD. Other studies have focused on clinical data and, in particular, on cognitive function. For example, a meta-analysis found an inverse correlation between MMSE score and homocysteine level.

Thus, our study seeks to evaluate the impact of hyperhomocysteinemia on the severity and early onset of AD, while knowing the presence or absence of genetic risk factors associated with AD.

Inclusion Criteria:

• Clinical diagnosis of Alzheimer's disease
• Positive CSF biomarkers
• age of onset < 75 years
• already benefited from a previous research of Alzheimer's disease genetic features (PSEN1, PSEN2, APP, APOE)
• already benefited from a previous research of homocysteine cycle (monocarbon metabolism) by complete exome/clinical exome or panel

Exclusion Criteria:

• patient refusal

Patients with Alzheimer's disease with positive CSF biomarkers, age of onset < 75 years, and having already benefited from a previous research of Alzheimer's disease genetic features (PSEN1, PSEN2, APP, APOE) and homocysteine cycle (monocarbon metabolism) by complete exome/clinical exome or panel