Case For More Studies To Gauge The Role of ε4 Allele in the Onset of Alzheimer’s
Apolipoprotein E (ApoE) alleles - ε2, ε3, ε4, are the chief determinants of Alzheimer’s Disease(AD). Past studies have shown that individuals carrying the ε4 allele are at greater risk of developing AD. Those carrying ε3 have shown no marked predisposition to AD while ε2 confers on its carriers, a distinctive advantage in protection against amyloid deposits and dementia.
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However, the effect of the ε4 allele on middle-aged subjects and declining cognitive function needs further research. In light of recent studies, evidence has been inconclusive about the impact of the ε4 allele on cognition in middle age. ε4+ as well as ε4- subjects have more or less similar performance scores on various neuropsychological tests. Also, there’s no marked difference in performance as compared to ε2 and ε3 carriers. On the other hand, some ε2 carriers have scored lower on a few tests compared to carriers of ε3 and ε4 - casting doubts on the hypothesis about the benefits of ε2.
Most of these recent studies work on the three widely recognized theoretical assumptions:
- the cognitive phenotype hypothesis
- the prodromal hypothesis
- the antagonistic pleiotropy hypothesis.
In the absence of any conclusive evidence supporting these hypotheses, further studies need to be more streamlined, with larger sample sizes and more variation in test subjects' educational, economic, and social backgrounds. Assessing the interaction between these alleles and other biological markers like hormones, health conditions, history of diseases, and genetic disorders should also be factored in.
Test tasks set to determine cognition, recall, and response rate also need a rehaul. Tasks should incorporate more sensitivity to avoid ceiling bias, collate data from longitudinal studies, test for variation in gene dosage for both ε2 and ε4, explore the advantages/disadvantages of ε2, and deliver results with consistency to arrive at accurate facts.
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APOE Alleles Image Source - Interchopen
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