From the Guidelines
The PSEN1 gene has the highest risk for early-onset Alzheimer's disease (AD) due to its complete penetrance, meaning that all individuals who have a PSEN1 mutation will develop AD if they live a normal lifespan 1.
Key Points
- PSEN1, PSEN2, and APP are the three known deterministic genes associated with autosomal dominant early-onset AD (EOAD) 1.
- Mutations in PSEN1 and APP are associated with complete penetrance, while mutations in PSEN2 show 95% penetrance 1.
- The age of onset can vary more than 20 years within the same family, and clear genotype-phenotype correlations cannot typically be made for the three causative genes 1.
- Genetic counseling and testing for AD should be offered in situations where a symptomatic individual has EOAD, or there is an autosomal dominant family history of dementia with one or more cases of EOAD 1.
- The Alzheimer Disease & Frontotemporal Dementia Mutation Database should be consulted before disclosure of genetic test results, and specific genotypes should not be used to predict the phenotype in diagnostic or predictive testing 1.
From the Research
Gene Associated with Early-Onset Alzheimer's Disease
The gene with the highest risk for early-onset Alzheimer's disease (AD) is associated with mutations in the presenilin 1 (PSEN1) gene, as it is the most frequently mutated gene in autosomal dominant early-onset AD, with a mutation frequency of 18 to 50% 2.
Key Genes Involved in Early-Onset AD
Some of the key genes involved in early-onset AD include:
Genetic Mutations and Risk
Mutations in these genes, particularly PSEN1, have been identified as major genetic causes of early-onset Alzheimer's disease (EOAD) 4. The apolipoprotein E (APOE) epsilon4 allele has also been identified as a risk factor for both late-onset and early-onset AD 3, 2.
Genetic Screening and Diagnosis
Genetic screening, including whole exome sequencing, has been successfully used to identify mutations and diagnose early-onset AD 4, 5. Understanding the genetic mechanisms of AD is essential for the development of diagnostic processes and therapeutic targets 3, 5, 6.