Scientists have discovered two types of genes involved in the development of Alzheimer's disease, risk genes and deterministic genes.
Risk genes increase the probability of developing Alzheimer's disease; they do not guarantee its development.
- Apoliprotein E (ApoE) gene:
The most prominent risk gene is a member of the ApoE (apoliprotein E) family and is found on chromosome 19. ApoE is essential for the breakdown of lipids.
There are three types of ApoE genes; ApoE-e2, ApoE-e3 and ApoE-e4. ApoE-e4 is considered a risk gene for Alzheimer's disease, whilst ApoE-e2 is thought to offer protection from Alzheimer's Disease (Saunders, 2000).
Scientists are currently unsure why ApoE-e4 is a major risk factor in developing this disease. However, it is thought that apoliprotein E catalyses the breakdown of beta-amyloid, and that each type of the apoliprotein has a different efficiency to do this (Jiang et al, 2008). ApoE-e4 having the lowest efficiency, therefore leading to a build up of beta-amyloid in the brain and the formation of amyloid plaques.
- SORL1 gene:
Discovered in 2007, SORL1 is a receptor for apoliprotein E and it is considered a risk gene for Alzheimer's Disease. Low levels or mutant forms of SORL1 have been proven to increase beta-amyloid protein, leading to the formation of amyloid plaques.
Deterministic genes are genes that when mutated guarantee the development of a gene.
Three deterministic genes have been discovered in the development of Alzheimer's disease. These deterministic genes code for amyloid precursor protein (APP), presenilin-1 (PSEN-1) and presenilin-2 (PSEN-2), mutations in these genes lead to early onset Alzheimer's disease.
- Amyloid precursor protein (APP) gene:
The APP gene codes for APP, which is a integral membrane protein found primarily in neurons. When APP undergoes proteolysis it forms beta-amyloid protein. High levels of mutant APP has been proven to cause Alzheimer's Disease.
- PSEN1 and PSEN2 genes:
PSEN1 gene is located on chromosome 14, and codes for presenilin 1 (PS-1). Whilst, PSEN2 gene is located on chromosome 1, and codes for presenilin 2 (PS-2). Presenilin is a component of gamma secretase that is responsible for cutting APP. Beta-amyloid formed by the cutting of APP, is at most risk of causing Alzheimer's Disease when it is cut to a length of 42 amino acids, as it is more likely to aggregate. A mutatant form of PS-1 and PS-2 leads to an increase in beta-amyloid 42.