Alzheimer's disease (AD) is a progressive, irreversible
neurodegenerative disease and it is the leading cause of dementia. According to the
National Institute on Aging (NIA), AD is characterized by the intracellular aggregation of
Neurofibrillary tangle (NFT), which consists of hyper-phosphorylated
Tau protein, and by extracellular accumulation of
amyloid beta. Symptoms of AD include memory loss, cognitive decline, increased anxiety or aggression. The disease can be fatal.
Prevalence and incidence In 2020, approximately 5.8 million Americans over the age of 65 (or approximately 1 in 10 people in that age group) had AD. Risk for the disease increases with age, with 32% of people over the age of 85 living with AD. The number of AD patients will increase rapidly in the coming years, as the majority of the Baby Boomer generation has reached the age of 65 and the population of Americans over the age of 65 is projected to grow to 88 million by 2050. African Americans are about twice as likely to have AD as Caucasians, and the prevalence of AD in African Americans is higher than that in any other racial group. 21.3% of African Americans over the age of 70 have AD, a much higher prevalence than the national average. The risk of dementia (not limited to AD) among relatives of African Americans who have AD is 43.7%,
Neuroinflammation Neuroinflammation has been suggested to play a prominent role in the pathogenesis of AD due to the discovery of increased levels of inflammatory markers in AD patients; There is an increased level of inflammation markers, such as IL-1β, MIG, TRAIL, and FADD, in the brains of African Americans compared to Caucasians. Furthermore, the NLPR3
inflammasome that is thought to be critically involved in AD has increased activation in African Americans. Evidence also suggests a stronger association between the level of IL-8 (an inflammation marker) and cognitive performance in African Americans than Caucasians.
Cognitive decline and mild cognitive impairment The incidence of
Mild cognitive impairment (MCI), an indicator of disease onset in early stages, is higher in African American populations compared to White populations. However, risk factors of AD, such as diabetes and cardiovascular diseases, are not associated with an increased risk of MCI in African Americans. The rate of cognitive decline in MCI also appears to be faster in African Americans. But the majority of African American patients with MCI are considered nonamnestic, particularly in language and executive function, so diagnosis of MCI among African Americans could lead to early interventions that delay further cognitive decline.
Biomarkers A
biomarker is a measurable indicator of a disease's state and the status of the body. It is helpful in disease diagnosis, tracking progression, and monitoring the response to treatment. Developing reliable biomarkers is an important part of AD research because an early, correct clinical diagnosis would allow physicians to initiate treatment with symptomatic and disease-modifying drugs. Biomarkers alone cannot show if a person might have AD, as they are only part of the assessment; however, they can help physicians and researchers identify potential risk factors, detect early brain changes, and track responses to drugs and other non-pharmacological interventions. Tau PET detects the abnormal accumulation of tau protein, which is also a hallmark of AD. It is not commonly used in medical practice to diagnose patients, Some are unchangeable, like age and heredity, but some are environmental factors that can be modified to influence disease onset and progression.
Genetics There are two categories of genes influencing AD: risk genes, which increase the risk of developing AD but do not guarantee that the disease will develop, and deterministic genes that actually cause AD. Fewer than 1% of AD cases are caused by deterministic genes. suggesting that further research on the genetics of African American AD patients is necessary to understand the disease pathologies.
APOE ε4 The
Apolipoprotein E (APOE) is a protein involved in transportation of fats, like cholesterol, in the bloodstream.
APOE comes in three different forms, or
alleles: ε2, ε3, and ε4. Each person carries two
APOE alleles, one from each biological parent, resulting in six possible pairs: ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4. and early AD onset.
APOE ε4 is the strongest risk gene that has been discovered, Yet, African Americans with
APOE ε4 are at a lower risk of developing AD than other racial groups, However, for individuals without the
APOE ε4 allele, the cumulative risk of AD was four times higher for African Americans than Whites (risk ratio: 4.4).
ABCA7 ABCA7 is a member of the highly conserved family of
ATP-binding cassette (ABC) transporters, which use energy from
ATP hydrolysis to transfer molecules from the inside to the outside of cell membranes. The
ABCA7 gene is among the top ten risk genes for AD. Risk from the
ABCA7 gene is the strongest for African Americans, whose risk due to the gene has an effect size approaching that of
APOE. Furthermore, deleterious
ABCA7 alleles can cause protein loss-of-function, and these loss-of-function mutations increase risk of AD by 80% in African Americans. The mechanism of the role played by ABCA7 in AD pathogenesis remains unknown. A leading hypothesis is that ABCA7 regulates APP processing and amyloid beta clearance. Several rare mutations on
APP cause
Familial Alzheimer's disease (FAD), a subset of early-onset AD (in which patients develop symptoms by their early 40s), in only a few hundred extended families worldwide. FAD accounts for fewer than 1% of all AD cases.
PS-1 and PS-2 Presenilin 1 (PS1) and Presenilin 2 (PS2) are the cleaving enzymes in the γ-secretase complex. There are close to 200 mutations on PS1 and PS2 combined that cause early-onset Alzheimer's disease, and they predominantly alter the amino acids in their transmembrane domains. These mutations increase the production of the less soluble, more toxic Aβ42. In addition, factors (like
obesity) that increase risk for cardiovascular diseases are also associated with an increased risk for AD. Rates of severe obesity are higher among African Americans (12.1%) than Hispanics (5.8%) and Whites (5.6%). Cardiovascular diseases and obesity can be managed and countered through exercise, with regular exercise also reducing the risk of developing AD by 45%. Exercise also has a greater positive effect in cognitive function in AD patients who are
APOE ε4 carriers compared to non-carriers. Conversely,
APOE ε4 carriers with a sedentary lifestyle show a greater amyloid beta deposition compared to non-carriers. There is also a greater prevalence of risk factors related to diabetes among African Americans, contributing to the higher burden of diabetes and higher risk of AD.
Treatments There is currently no cure for AD, but there are drugs approved by the
Food and Drug Administration (FDA) to manage disease progression. Treatments can be divided into either symptomatic drugs, meaning that they only affect the symptoms and not the underlying cause, or disease-modifying drugs, meaning that they could change the disease progression over time. == Socioeconomic disparities ==