Alzheimer’s Risk Factor

Alzheimer’s disease is one of the most heritable common, complex disorders, with a heritability of 60% to 80% and is one of the few diseases for which a single susceptibility gene nl .APOE, gives rise to a substantial risk.

ApoE is a serum protein and is involved in the transport, storage and metabolism of cholesterol. The ApoE-gene has three more frequently occurring alleles, E2, E3 and E4, which encode the protein isoforms ApoE2, E3 and E4. Approximately 15 per cent of the population carries an APOE gene variant that causes their bodies to produce a lipoprotein known as apolipoprotein (Apo) E4. About 95% of the Caucasian population carries at least one E3 allele, 27% an E4 allele and 16% an E2 allele. People who inherit the E4 gene variant from both parents have a tenfold risk of developing the diseasee3 is the most common allele

The APOE gene is located on the long (q) arm of chromosome 19 at position 13.2. More precisely, the APOE gene is located from base pair 50,100,878 to base pair 50,104,489 on chromosome 19.

Research has uncovered a molecular mechanism that links the susceptibility APOE E4 gene variant to the onset of Alzheimer’s disease. The ApoE4 (along with other apolipoproteins) attaches itself to a particular receptor on the surface of brain cells. That receptor, in turn, adheres to a protein known as amyloid precursor protein. The brain cells then transport the entire protein mass inside. Once inside, proteases (cutting enzymes) attack the amyloid precursor protein to create protein fragments that are believed to cause the cell death, memory loss and neurological dysfunction characteristic of Alzheimer’s when present in the brain for long periods of time.

Approximately 1 in 7 people carry the E4 variant of ApoE; the remainder of the population carry variations known as E2 and E3. These individuals have a markedly lower incidence of Alzheimer’s than those who carry the E4 gene. New studies found that ApoE4 produced more protein fragments than did E2 or E3.