Chromosome 19, ApoE gene

APOE has three common isoforms, namely, E2, E3, and E4, which are coded by the APOE alleles e2, e3, and e4 at a single locus on chromosome 19. The APOE gene has been extensively examined in populations worldwide for its association with an increased risk for CAD and AD [25, 34] and has also been evaluated in centenarian populations in different studies. 

The genetic basis for the more common late-onset AD appears more complex. Genetic susceptibility is more sporadic and it may be more dependent on environmental factors.9 The apolipoprotein E (apo E) gene on chromosome 19 has been identified as a strong risk factor for late-onset AD. There are three variants of apo E however, carriers of two or more of the apo E4 allele have an earlier onset of AD (approximately 6 years earlier) compared with non-carriers.9 Only 50% of AD patients have the apo E4 allele, thus indicating it is only a susceptibility marker. 

In 1993/1994 a series of publications caused a stir in the AD research community, since for the first time they linked a specific neuropathological process in late-onset AD to a genetic marker. Researchers looking at the composition of plaques found that the protein apolipoprotein E (ApoE) was associated with p-amyloid in the cerebrospinal fluid (CSF) of AD patients (Strittmatter et al., 1993). The gene for ApoE is on the same human chromosome (number 19) which was a risk factor in some AD pedigrees. The gene for ApoE comes in three versions (alleles) Apo s2, Apo s3 and, most importantly, Apo s4 these result in three slightly different variants of the protein. Humans carry two versions of the allele and so can have none, one or two of any of the versions of the Apo... 

It is clear from family studies that apo(a) gene polymorphism is a consequence of the autosomal codominant Mendelian inheritance of multiple alleles operating at a single chromosomal locus (G7, U4, U6). In families where this simple inheritance pattern was not followed, the existence of a null allele has been postulated (U4, U6). A null allele frequency of 6% was estimated for the subjects... 

Genes coding for APO-E are associated with different risks for Alzheimer s disease. There are three alleles (or copies) of the gene coding for this apolipoprotein which are called E2, E3, and E4. For example, a gene on chromosome 19 that codes for APO-E is linked to many cases of late-onset Alzheimer s disease. Moreover, APO-E is associated with cholesterol transport and involved with other neuronal functions, including repair, growth, and maintenance of myelin sheaths and cell membranes. 

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