Late-onset Alzheimer´s disease - APOE gene
Alzheimer's disease is a neurodegenerative disorder that affects the central especially cholinergic neurons in the hippocampus, the area of neurocortical association and other limbic structures. Neuropathological changes include cortical atrophy, extracellular neuritic plaques, and intraneuronal neurofibrillary tangles amyloid deposits in the walls of cerebral arteries. It is characterized by a progressive loss of cognitive function, comprising the recent memory, abstract reasoning, concentration, visual perception and spatio function. Eventually, patients can not work and need continuous supervision. At the end of the disease most patients develop rigidity, mutism and incontinence.
Alzheimer's disease late onset usually develop after age 65. Unlike what happens with early - onset familial cases - see early familial Alzheimer's Disease ... - genes involved in Alzheimer's disease late are not decisive. So far, the only gene significantly associated with this form of the disease is the APOE gene, located on the long arm of chromosome 19 (19q13.2). This gene encodes the protein apolipoprotein E, a protein is combined with lipids in the body to form lipoproteins. Lipoproteins are responsible for transporting cholesterol and other fats through the bloodstream. Maintaining normal cholesterol levels is essential for the prevention of cardiovascular disease, including heart attack and stroke. Three common protein isoforms (?2, ?3 and ?4), which are distinguished by the presence of cysteine or arginine amino acids at 112 and 158 of APOE positions are known.
Alzheimer's disease late onset presents a strong association with the ?4 allele, especially when it is in homozygotes. ?4 version of the APOE gene increases an individual 's risk of developing Alzheimer's disease late onset. The ?4 APOE may also be associated with an earlier onset of memory loss and other symptoms. Although it is unclear how the APOE ?4 allele is associated with the risk of Alzheimer's disease, it is believed that this allele is associated with a greater number of amyloid plaques in the brain tissue of people affected. An accumulation of beta amyloid peptide and amyloid plaques can cause toxic death of neurons and progressive signs and symptoms of this disease.
The inheritance pattern of Alzheimer's disease late onset is uncertain. People who inherit one copy of the APOE ?4 allele are more likely to develop the disease, while those who inherit two copies of the allele have an even greater risk. It is important to note that people with the APOE e4 allele inherited an increased risk of developing Alzheimer's disease, not the disease itself. Not all people with Alzheimer's disease have the ?4 allele, and not all people who have the ?4 allele will develop the disease.
Tests performed in IVAMI: in IVAMI detect the presence of arginine residues at amino acids 112 and 118, APOE ?4 allele own, linked to the development of late AD, by PCR amplification and subsequent direct sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).