Apolipoprotein E and alpha‐1 antichymotrypsin polymorphism genotyping in Alzheimer's disease and in dementia with Lewy bodies Distinctions between diseases

Lamb, Helen; Christie, J. E.; Singleton, AB; Leake, A.; Perry, RH; Ince, PG; McKeith, Ian G.; Melton, Lisa; Edwardson, J. A.; Morris, Christopher M.

doi:10.1212/wnl.50.2.388

Cited by 28 publications

(21 citation statements)

References 2 publications

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“…Although this association was con®rmed in a group of Japanese AD patients [Yoshiiwa et al, 1997], several other groups have not found this association in Caucasian AD patients Muller et al, 1996;Nacmias et al, 1996;Talbot et al, 1996;Didierjean et al, 1997;Helisalmi et al, 1997;Morgan et al, 1997;Murphy et al, 1997;Lamb et al, 1998]. Also, Muramatsu et al [1996] found a nonsigni®cant trend for the AA genotype in Japanese AD patients, which was signi®cant only in non-E4 individuals.…”

Section: Discussionmentioning

confidence: 94%

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

et al. 2001

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Alzheimer disease (AD) is an emotionally devastating and exceptionally costly disease. Apolipoprotein E (APOE) is a major risk factor gene for AD regardless of age of onset or family history. However, this association may not be as strong or consistent in ethnic groups such as African Americans, raising the possibility of other modifier gene(s). In a group of African American AD patients, a significantly increased risk of AD was associated with two E4 alleles (OR = 5.6; 95% CI = 1.5-21.0) or one E4 allele (OR = 2.5; 95% CI = 1.3-5.0) when compared to E3/E3 genotype, and there was a significant lowering of age of onset for affecteds with E4/E4 genotype as compared to one E2 allele (P = 0.02) or all others (P = 0.03). We also found a significant increase in age of onset with the -308 #2 (A) allele of TNF when compared to AD cases with no #2 allele. A significant increase in age was also demonstrated with the #2 allele (99 base pairs) of the microsatellite TNFa, located approximately 10.5 kb upstream of TNF. When these two alleles were combined with the TNF -238G (#1) allele to give a haplotype, the significant increase in age was still demonstrated. Polymorphisms in the APOE promoter and six other candidate genes did not appear to demonstrate any significant association with our African American AD patients. Our results confirm the established association of APOE4 to AD observed in several ethnic groups, including African Americans. In addition, TNF appears to have some modifying effect in AD, primarily on age of onset, or it could be in linkage disequilibrium with a modifier locus nearby.

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Section: Discussionmentioning

confidence: 94%

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

et al. 2001

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“…Kamboh et al [83] genotyped subjects at a di-allelic polymorphism in a region of the ACT gene coding for either threonine (T allele) or alanine (A allele); they found that the combination of the ACT/AA genotype and the APOE Â4 allele increased the risk of late-onset AD 2-to 3-fold. Subsequent reports did not support this effect of the ACT polymorphism alone or in combination with the APOE Â4 allele [84].…”

Section: Bleomycin Hydrolasementioning

confidence: 94%

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Combarros

Alvarez-Arcaya²,

Sánchez-Guerra³

et al. 2002

Dement Geriatr Cogn Disord

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The genetics of Alzheimer’s disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the Ε4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-β, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE Ε4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.

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“…PCR amplification of the two polymorphic sites which determine APO E Â genotype (codons 112 and 158) was performed using oligonucleotide primers; forward 5)-TCCAAGGAGCTGCAGGCGG-CGCA-3) and reverse 5)-ACAGAATTCGCCCCGGCCTGGTA-CACTGCCA-3) using previously described methods [22,28,29].…”

Section: Apo E Genotypingmentioning

confidence: 99%

“…Tissue blocks from the formalin-fixed right hemisphere were taken from the frontal, temporal, occipital and parietal cortex, embedded in paraffin wax and sections were cut at 10 Ìm thickness on a microtome [22]. Routine histology was carried out on the four cortical regions and SP and NFT were stained with Von Braunmühl's method and Palmgren's silver method [30], respectively, for AD diagnosis and quantification of SP and NFT.…”

Section: Neuropathological Examinationmentioning

confidence: 99%

“…The aim of this study is to examine the influence of APO E genotype in a large UK population of DLB patients and to compare it with the findings in AD in order to determine if there are any differences between the effect of APO E in the two diseases, as have been documented previously [22,23]. We have tested the hypothesis that the Â4 allele is a significant risk factor for DLB and conversely that the Â2 allele is protective.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Neuropathological Correlates of Apolipoprotein E Genotype in Dementia with Lewy Bodies

Singleton

Wharton

O’Brien

et al. 2002

Dement Geriatr Cogn Disord

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Dementia with Lewy bodies (DLB) represents the second commonest cause of dementia in the elderly following Alzheimer’s disease (AD). Whilst the presence of Lewy bodies is essential, DLB shares with AD the presence of senile plaques (SP), but neurofibrillary tangles (NFT) are not a necessary feature. The apolipoprotein E (APO E) Ε4 allele is the most consistently associated genetic risk factor for AD and has also been shown to associate with DLB. We have therefore analysed the APO E Ε4 allele in a large series of DLB cases coming to autopsy to: (1) determine if the Ε4 allele describes a similar risk in DLB development as in AD and (2) determine how APO E Ε4 allele status correlates with clinical and neuropathological findings in DLB, and in AD, as an indication of the role of APO E in underlying disease biology. Both DLB and AD share an increased Ε4 allele frequency, though in DLB the Ε2 allele frequency is not reduced and there is a relative lack of Ε4 homozygotes. In contrast to previous studies, no association of the Ε4 allele with age at onset or duration of disease was found in either disorders. In DLB cases, overall a significantly shorter duration of illness was observed when compared with AD cases, though no significant effect of the Ε4 allele on disease onset or duration was seen. The survival rate was reduced by the presence of the Ε4 allele in DLB, as with AD. No effect on SP or NFT counts was seen with the Ε4 allele, though DLB cases showed a lower SP burden in addition to the expected lower NFT counts. This study demonstrates that DLB shares the APO Ε4 allele with AD as a common risk factor, but that there are differences in the way the Ε4 allele affects the phenotypic expression of disease.

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Apolipoprotein E and alpha‐1 antichymotrypsin polymorphism genotyping in Alzheimer's disease and in dementia with Lewy bodies Distinctions between diseases

Cited by 28 publications

References 2 publications

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Clinical and Neuropathological Correlates of Apolipoprotein E Genotype in Dementia with Lewy Bodies

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