Apolipoprotein E ε4 Allele Frequency and Age at Onset of Alzheimer’s Disease

Abstract

The age distribution of the Ε4 allelic form of the apolipoprotein E gene (APOE) was investigated in 630 patients with Alzheimer’s disease (AD) with onset age ranging from 35 to 90 years. Overall, mean age at onset in APOE Ε4 allele bearers was significantly later than that in nonbearers. However, when stratified into early onset AD (EOAD) and late onset (LOAD) groups, mean age at onset in EOAD cases bearing APOE Ε4 allele was later than that in those EOAD cases without Ε4 allele, whereas in LOAD mean age at onset in cases bearing APOE Ε4 allele was earlier than in those without Ε4 allele. When analysed by decade, it was observed that 37% of the total number of APOE Ε4 allele bearers, and 43% of total number of cases with APOE Ε4/Ε4 genotype fell into the 60–69 years age class. Hence, APOE Ε4 allele frequency, at 0.44, was highest in the 60–69 years age class, progressively decreasing either side of this age group. APOE Ε4 allele therefore has its maximum impact between onset ages of between 60 and 70 years.

Neuropsychological Performance and Conversion to Alzheimer’s Disease in Early- Compared to Late-Onset Amnestic Mild Cognitive Impairment: CREDOS Study

“…These results are consistent with previous reports suggesting that the ε4 allele was a definite biological risk factor for AD and may increase the risk of developing EOAD [43,44]. One recent study revealed that the frequency of ε4 homozygotes was highest in the group of AD with an age at onset of 60-69 years which may further support our result of a higher frequency of ε4 homozygote in the EOMCI group [45].…”

Apolipoprotein E ε4 Prevalence in Alzheimer’s Disease Patients Varies across Global Populations: A Systematic Literature Review and Meta-Analysis

“…APOE4 has been associated with about 65–75% of sporadic AD, but may be attributable to up to 20% of all dementias [5,6,7]. Furthermore, in a 1997 meta-analysis, the presence of an E4 allele decreased age at onset and increased the risk of disease as a gene dose, especially in patients with a disease onset between 40 and 60 years [8]. …”

The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

“…Several studies report a higher prevalence of the APOE-4 allele in VaD patients, patients with mixed AD and VaD, and in post-stroke dementia [12,28,59,60] . Other studies found no evident role of APOE-4 in the pathophysiology of VaD or dementia after stroke [42-44, 49, 61-63] , which is in line with our results.…”