Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which is the main component of amyloid plaques. Some of the mutations merely alter the ratio between Aβ42 and the other major forms—particularly Aβ40—without increasing Aβ42 levels. Two other genes associated with autosomal dominant Alzheimers disease are ABCA7 and SORL1.Most cases of Alzheimers are not inherited and are termed sporadic Alzheimers disease, in which environmental and genetic differences may act as risk factors. Most cases of sporadic Alzheimers disease in contrast to familial Alzheimers disease are late-onset Alzheimers disease (LOAD) developing after the age of 65 years. Less than 5% of sporadic Alzheimers disease have an earlier onset. The strongest genetic risk factor for sporadic Alzheimers disease is APOEε4. APOEε4 is one of four alleles of apolipoprotein E (APOE). APOE plays a major role in lipid-binding proteins in lipoprotein particles and the epsilon4 allele disrupts this function. Between 40 and 80% of people with Alzheimers disease possess at least one APOEε4 allele. The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes. Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance.
When adjusted for age, both sexes are affected by Alzheimers at equal rates. In the United States, the risk of dying from Alzheimers disease in 2010 was 26% higher among the non-Hispanic white population than among the non-Hispanic black population, and the Hispanic population had a 30% lower risk than the non-Hispanic white population. However, much Alzheimers research remains to be done in minority groups, such as the African American and the Hispanic/Latino populations. Studies have shown that these groups are underrepresented in clinical trials and do not have the same risk of developing Alzheimers when carrying certain genetic risk factors (i.e. APOE4), compared to their caucasian counterparts.The prevalence of Alzheimers disease in populations is dependent upon factors including incidence and survival. Since the incidence of Alzheimers disease increases with age, prevalence depends on the mean age of the population for which prevalence is given. In the United States in 2020, Alzheimers dementia prevalence was estimated to be 5.3% for those in the 60–74 age group, with the rate increasing to 13.8% in the 74–84 group and to 34.6% in those greater than 85. Prevalence rates in some less developed regions around the globe are lower. As the incidence and prevalence are steadily increasing, the prevalence itself is projected to triple by 2050. As of 2020, 50 million people globally have AD, with this number expected to increase to 152 million by 2050. History
The ancient Greek and Roman philosophers and physicians associated old age with increasing dementia.