[Genetic aspects of Alzheimer disease] (original) (raw)
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Annals of Neurology, 1995
Numerous studies have shown that the risk of Alzheimer's disease (AD) is associated with the dose of the € 4 allele of apolipoprotein E (ApoE). However, more than one third of AD patients lack ~4 and many persons having ~4 survive cognitively intact to old age. We evaluated the lifetime risk of disease in 3,999 first-degree relatives of 549 probands who met the criteria for probable or definite AD and whose ApoE genotypes were known. ApoE genotypes for relatives were not determined. After age 65 the risk among relatives was proportional, as much as 7 to 10% at age 85, to the number of ~4 alleles present in the proband. Risks to relatives of ApoE 212 and 2/3 probands were nearly identical at all ages to risks for relatives of ApoE 3 / 3 probands. The expected proportion of relatives having at least one € 4 allele was calculated for each genotype group based on the distribution of parents, sibs, and offspring in the sample. Among relatives in the ApoE 3 / 3 group, the lifetime risk for AD by age 90 was three times greater than the expected proportion of ~4 carriers, suggesting that factors other than ApoE contribute to AD susceptibility. Furthermore, the 44% risk of AD by age 93 among relatives of ApoE 414 probands indicates that as many as 50(%' of people having at least one ~4 allele do not develop AD. We also found that among male relatives, risk of AD in the ApoE 314 group was similar to that for the ApoE 313 group but significantly less than the risk for the ApoE 414 group. In contrast, among female relatives the risk for the ApoE 314 group was nearly twice that for the ApoE 3 / 3 group and identical to the risk for the ApoE 414 group. These findings are consistent with a sex-modification effect of the E4 isoform on disease susceptibility. SA, Volicer L. Wells JM, van Broeckhoven C, G r o w d o n JH. Haines JL. Apolipoprotein E genotype i n patients with Alzheimer's disease: implications for the risk of dementia among relatives. Ann Neurol 1995;38:797-808
Genetika, 2001
Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = ...
Annals of the New York Academy of Sciences, 1996
Strittmatter er al. ' reported in 1993 that the APOE €4 allele was associated with an increased risk for developing Alzheimer's disease (AD) in a set of families who appear to have late-onset familial AD. Several groups, including our own, rapidly demonstrated that the overrepresentation of APOE €4 applied to sporadic AD as Given that inheritance of APOE €4 is a risk factor for AD, our goal was to address two important questions: (1) Are there differences in the clinical course or the pathology of the disease if a patient has inherited APOE ~4 ?
Frequency of the apolipoprotein E ε2 allele is diminished in sporadic Alzheimer disease
Neuroscience Letters, 1994
Recent data have demonstrated genetic disequilibrium between inheritance of the apolipoprotein E (apoE) e4 allele and increased risk of Alzheimer disease. We tested the idea that inheritance of other allelic variations of apoE might also increase or decrease the risk of developing Alzheimer disease. We studied apoE genotypes in a large clinic based population of Alzheimer disease patients and age-compatible, tested control individuals. We confirm the genetic disequilibrium between apoE e4 and Alzheimer disease and now report that inheritance of apoE e2, another common variant of the apolipoprotein E gene, is negatively associated with risk of developing Alzheimer disease.
Apolipoprotein E ?2 does not increase risk of early-onset sporadic Alzheimer's disease
Annals of Neurology, 1997
We examined the association of apolipoprotein E (ApoE) genotype and the risk of early-onset Alzheimer's disease (AD) in 209 white early-onset sporadic cases (43% male) and 303 white controls (48% male) of similar age distribution. The risk of AD was significantly increased, relative to the 313 genotype, in people with the 414, 314, and 214 genotypes, controlling for age at time of examination and sex. The 213 genotype reduced slightly the risk of AD, although the effect was not statistically significant.
Apolipoprotein eϵ4, other risk factors, and course of alzheimer’s disease
Biological Psychiatry, 1999
Background: The ⑀4 allele of apolipoprotein E (apoE ⑀4) is associated with late-onset Alzheimer's disease (AD), but its relationship to various aspects of AD has become increasingly unclear. We studied the relationship of apoE genotype in AD to educational attainment, history of heart disease or head injury, age of onset, gender, severity of illness, depression, psychotic symptoms, rate of dementia progression, and time from initial evaluation to nursing home placement. Methods: ApoE ⑀4 genotype was determined for 97 clinically diagnosed AD patients and 61 neuropathologically confirmed cases of AD. Results: Presence of one or more ⑀4 alleles occurred in 66% of AD cases as compared with 27% in control subjects (allele frequency was .40 for AD, .15 for control subjects). Among AD subjects there was no significant relationship between ⑀4 alleles and educational attainment, history of heart disease, head injury, age of onset, severity of illness, depression, history of depression, rate of dementia progression, or time to nursing home placement. Marginal correlations emerged between number of ⑀4 alleles, and delusions (p ϭ .05) and hallucinations (p ϭ .05). There was a trend toward increased ⑀4 homozygosity in patients with onset between ages 65 and 70 years. Conclusions: We did not find that individuals with one or two apoE ⑀4 alleles differed significantly in clinical course of AD from those without ⑀4 except for a trend toward increased psychotic symptoms in the group as a whole and an increase in ⑀4 homozygosity in patients with reported symptom onset in the late 60s.