Epidemiological studies have revealed a correlation between the apo-E4 allele and risk of developing Alzheimer’s disease. About 80% of familial and 64% of sporadic Alzheimer’s disease late-onset cases have at least one apo-E4 allele, compared to 31% of control subjects. The apparent risk is dose dependent. In one study, 91% of E4/E4 homozygous individuals from families with diagnosed Alzheimer’s disease were affected, while only 48% of E3/E4 patients and approximately 20% of E2/E3 or E3/E3 patients were affected. Three hypotheses are being considered to explain this correlation. One suggests that apo-E4 associates more readily than the other apoE isoforms with the amyloid protein to form deposits. Another hypothesis states that apoE4 does not associate properly with a microtubule associated protein termed tau. A third hypothesis is that the different forms of apoE have distinct effects on the growth and extension of axons after nerve injury.
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