Rationale for Correct Answer
The correct answer is: Most cases of Alzheimer's disease occur sporadically rather than through dominant inheritance, regardless of the age of onset
Alzheimer's disease is a complex and multifactorial neurodegenerative disorder that affects millions of people worldwide. The exact cause of Alzheimer's disease is not yet fully understood, but genetic and environmental factors are known to play important roles in its development.1,2
The vast majority of Alzheimer's cases are sporadic and of late-onset (after the age of 60 to 65). Dominantly inherited mutations in the amyloid pathway account for less than 1% of Alzheimer's disease cases. These cases usually present before the age of 60 to 65.1
Late-onset Alzheimer’s disease (LOAD) heritability is high, ranging from 58% to 79%. While LOAD etiology is multifactorial and driven by a combination of genetic and environmental factors, numerous genes have been implicated in contributing to LOAD.3
ApoE2 (decreases risk), ApoE4 (increases risk), and ApoE3, which is frequently used as a reference, are the most common ApoE alleles.4 Over 80 other AD-associated genes have been identified in non-Hispanic White populations (fewer have been found in other ethnic groups).5,6
References:
1. Armstrong R. Folia Neuropathol. 2019;57:87-105.
2. Kamboh MI. Neurotherapeutics. 2022;19:152-172.
3. Gatz M et al. Arch Gen Psychiatry. 2006;63:168-174.
4. Corder EH et al. Science. 1993;261:921-923.
5. Reitz C et al. Nat Rev Neurol. 2023;19:261-277.
6. Bellenguez C et al. Nat Genet. 2022;54:412-436.