genetics

Figure 1 The four genes and their respective chromosomes associated with Alzheimer’s disease.3

· Amyloid Precursor Protein (APP)

· Chromosome: 21q21

· Inheritance: Autosomal Dominant

· APP missense mutations have been found in 85 families, though only about 10-15% of these mutations account for the presence of early-onset familial AD.2

· This gene is an integral membrane protein and is concentrated in the synapses of neurons. Although its function is unknown it is associated with synapse formation regulation and the ability of the nervous system to adapt to changes in the environment.2

· Apolipoprotein E (APOE)

· Chromosome: 19q13.32

· Inheritance: Sporadic

· APOE plays a role in the metabolism of cholesterol and triglycerides throughout the body.2

· APOE comes in different alleles:  ε2, ε3, and ε4.

· ε2: rare, and is usually associated with a much later occurrence of Alzheimer’s disease when compared to someone with a different APOE gene.1

· ε3: this is the most common allele and doesn’t affect risk in this disease.1

· ε4: this gene increases the risk of getting the disease and at an earlier age. The most APOE ε4 genes one can have is 2 – the more you have the greater the risk.1

· Presenilin 1 (PSEN1)

· Chromosome: 14q24.2

· Inheritance: Autosomal Dominant

· Mutations in this gene are the most common cause of EOAD, accounting for 18-50% of familial cases.2

· The missense mutation in this gene causes the most severe form of EOAD, characterized by progressive dementia and parkinsonism.2

· PSEN1 forms the catalytic core of the γ-secretase complex.2

· Presenilin 2 (PSEN2)

· Chromosome: 1q42.13

· Inheritance: Autosomal Dominant

· Unlike PSEN1, missense mutations in this gene are a rare cause of EOAD, affecting individuals much later in life in comparison.2

· This gene is found highly expressed in neurons and the mutations associated affects the way in which APP is cut by γ-secretase.2

References:

1. Alzheimer's Disease Genetics Fact Sheet. (2015, August 30). Retrieved from https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet.

2. Bekris, L. M., Yu, C. E., Bird, T. D., & Tsuang, D. W. (2010). Genetics of Alzheimer disease. Journal of geriatric psychiatry and neurology, 23(4), 213–227. doi:10.1177/0891988710383571

3. Stavljenic–Rukavina, A. (2004). Molecular Mechanisms in Alzheimer's Disease.