Alzheimer’s disease: Description
Alzheimer’s disease (AD) is a degenerative disorder which affects a person’s cognition and behavior (dementia). This illness is caused by the brain degeneration and abnormal protein deposition in the brain cells. AD progresses for decades as the brain structures are gradually affected (sustain atrophy). Of note, Alzheimer’s disease is the most common cause of dementia and typically manifests in adults older than 65 years.
The disorder is considered to have a mixed etiology – the disease development is predisposed by both genetic and environmental factors. In sporadic cases of the disease there is no specific mutations, in small percentage of patients a specific genetic mutation is detected – this case of Alzheimer’s disease is referred to as familial in contrast to sporadic cases. This type of disease is called an early-onset AD and affects people from 30 to 65 years, comprising up to 5% of the AD cases.
Despite the fact that there is a strong link between the family history of the disease and the risk of disease development, those who don’t have ill relatives still may be at risk.
Single genes Alzheimer’s disease
Single genes causing Alzheimer’s are known to cause one type of early-onset Alzheimer’s disease, these genes are inherited as an autosomal dominant pattern, meaning that a child born from an ill mother/father who carries a mutation has a 50% risk of inheriting the defective gene and eventually will develop AD.
The genes involved in AD include the following:
- APP (amyloid precursor protein) gene located on chromosome 21 encodes the synthesis of the protein responsible for the neuronal development, formation of the synapses between the neurons and repair of the brain cells;
- PSEN-1 (presenilin-1) gene located on chromosome 14 is necessary for the APP processing via the γ-secretase complex;
- PSEN-2 (presenilin-2) gene located on chromosome 1 also plays a key role in the APP processing;
Susceptibility genes and increased risk of developing Alzheimer’s disease
On the other hand, there are also the susceptibility genes which increase the person’s risk of developing the AD but do not directly cause the disease.
Apolipoprotein E (APOE) gene located on chromosome 19 was found to be related to the risk of developing the Alzheimer’s. There are several forms (alleles) of this gene, of which APOE4 is considered to bear AD risk – approximately 14% of the general population are carriers of APOE4. In contrast, about 8% of the population have APOE2 which may even reduce the risk and be protective against AD when in fact APOE3 (present in 78% of the population) seems to be neutral regarding the Alzheimer’s disease risk. APOE4 gene may predispose the buildup of amyloid in the brain tissue – these deposits seem to be responsible for dementia. Every person has two copies of the APOE gene – those who have two copies of the mutant (APOE4) gene increase Alzheimer’s risk by 10-15 times, whereas carrying one mutant gene with one normal variant would double or triple the risk in comparison to a healthy person who has two APOE3 genes. On the other hand, as it was mentioned previously, APOE2 may be even protective, therefore, Alzheimer’s risk is reduced in APOE2 carriers by 40%.
Some other genes (up to 20 genes) were also investigated to be related to AD:
- ABCA7 (ATP binding cassette, subfamily A member 7);
- BIN1 (Bridging Integrator 1);
- CD2AP (CD-2-associated protein);
- CLU (allele C of the clusterin);
- CR1 (complement receptor 1);
- EPHA1 (EPH Receptor A1);
- MS4A4A/MS4A4E/MS4A6E (Membrane Spanning 4-Domains);
- PICALM (Phosphatidylinositol Binding Clathrin Assembly Protein);
- PLD3 (Phospholipase D Family Member 3);
- TREM2 (Triggering Receptor Expressed On Myeloid Cells 2);
- SORL1 (Sortilin-related receptor, L);
Since the APP gene is located on chromosome 21, those who have Down syndrome have 3 copies of the APP gene are at risk of developing Alzheimer’s disease. It is considered that about 25% of people who have Down syndrome will develop Alzheimer’s disease-like symptoms after the age of 35.
Genetic tests are available to identify one’s risks. Sometimes genetic testing can even predict the development of the disease with high certainty as long as the rare autosomal dominant mutations almost in 100% result in early-onset AD.
Our genetic test is helpful to identify whether a person is genetically predisposed to develop Alzheimer’s disease at some point and whether further investigations to exclude the disorder are needed.