Alzheimer’s disease [5 genes]

Alzheimer’s disease (AD) is the most common type of primary neurodegenerative dementia (60-80% of cases). Approximately 25% of patients with AD have two or more affected relatives. Among familial forms, only 5% have an early onset (<65 years of age). In these cases, the inheritance is autosomal dominant and is caused by pathogenic variants in the PSEN1 (30-70%), PSEN2 (<5%), and APP (10-15%) genes (Loy et al., 2014). The ℇ4 allele of the APOE gene represents a risk factor for AD (OR=2-3 in heterozygosity, OR=14,9 in homozygosity; Farrer et al., 1997), although the presence of the ℇ4 allele in APOE is not necessary or sufficient to produce the disease. Thus, although APOE genotyping may have some clinical use for supporting AD diagnosis, particularly in late-onset forms (>65 years), its use is not indicated in asymptomatic individuals.

Dementia poses an important social, health, and economic problem. Twenty-five percent of people older than 55 years of age have a family history of dementia. In 2016, it affected 46.8 million people worldwide. With exponential growth, it is expected that this number will rise to 131.5 million by 2050 (World Alzheimer Report 2016).

Diagnosis, prognosis and genetic counseling in affected individuals and family members.

Patients with clinical suspicion of Alzheimer’s disease.