Normal distribution of apolipoprotein E alleles in progressive supranuclear palsy

Anouti, Ahmad; Kg, Schmidt; Lyons, Kelly E.; Hubble, Jean; Schellenberg, Gerard D.; Golbe, L. I.; Lang, Anthony E.; Galvez-Jimenez, N.; Hershey, Linda A.

doi:10.1212/wnl.46.4.1156

Cited by 25 publications

(7 citation statements)

References 8 publications

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“…Previous studies have failed to find an association between ApoE ε4 and PSP 33, 34. Furthermore, it is known that PSP, like other degenerative disorders that occur with increased frequency in the elderly, can sometimes have amyloid deposits 35.…”

Section: Discussionmentioning

confidence: 99%

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy

Liu

Adamson

et al. 2001

Annals of Neurology

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Two extended haplotypes of the tau gene (H1 and H2) have been described. The frequency of H1 haplotype is increased in progressive supranuclear palsy (PSP). PSP is associated with filamentous tau lesions in neurons and glia, which are reportedly composed exclusively of tau isoforms with four repeats in the microtubule-binding domain (4R tau). To determine the influence of the tau haplotype on tau isoform composition and neuropathology, we studied 25 PSP cases and 6 Alzheimer's disease patients matched for age, sex, and postmortem delay. In the basal ganglia, tau and amyloid burdens were determined to see if there was an effect of concurrent Alzheimer-type pathology, and the ratio of 4R to 3R tau was measured in detergent-insoluble tau fractions. Insoluble tau from PSP was not composed exclusively of 4R tau. All brains had a mixture of 4R and 3R tau, but the ratio was different in Alzheimer's disease and PSP. In Alzheimer's disease there was less 4R than 3R tau, whereas the ratio was reversed in PSP. In PSP cases with concurrent Alzheimer-type pathology, the ratio of 4R to 3R was intermediate between Alzheimer's disease and PSP. The H1 haplotype had no effect on the 4R to 3R ratio or on tau and amyloid burdens. In summary, the H1 haplotype does not have a major influence on the pathological or biochemical phenotype of PSP.

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Section: Discussionmentioning

confidence: 99%

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy

Liu

Adamson

et al. 2001

Annals of Neurology

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“…Although findings have not been as consistent as in AD, an increase in the APOE E4 allele frequency has been variably observed in other forms of dementia, including diffuse Lewy body disease 27 -29 and vascular dementia. 30,31 But it does not appear to be an important risk factor in several other neurodegenerative processes, like progressive supranuclear palsy 32 and Parkinson's disease. 33,34 Some reports have suggested that APOE might also be a risk factor in FTD.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis

et al. 2002

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No definite genetic risk factor of non-monogenic frontotemporal dementia (FTD) has yet been identified. Several groups have examined the potential association of FTD with the apolipoprotein E (APOE) gene, but the results are inconsistent. Our objective was to determine whether APOE is a risk factor of FTD, using the largest series of patients with FTD and controls analysed so far (94 unrelated patients and 392 age and sex-matched controls), and a meta-analysis. Homozygosity for the E2E2 genotype was significantly associated with FTD (odds ratio (OR)=11.3; P=0.033, exact test). After stratification on familial history (FH) for FTD, the OR for E2E2 was still found significant when analysing only patients with a positive FH (OR=23.8; P=0.019). The meta-analysis, using 10 case -control studies with available genotype or allele information, comprising a total of 364 FTD patients and 2671 controls, including the patients of the present study, did not reach statistical significance even if the E2E2 genotype was more frequent in patients than in controls (0.018 vs 0.006, respectively). Because of studies heterogeneity (Mantel-Haenszel statistics: P=0.004), we analysed on one hand the neuropathologically-confirmed studies, and on the other hand the clinical-based studies. In the neuropathologically-confirmed studies (Mantel -Haenszel statistics: P=ns), we found a significant increase of the E2 allele frequency in FTD patients (OR[E2 vs E3]=2.01; 95% CI=1.02 -3.98; P=0.04). The same result was found in the clinical-based studies, but studies heterogeneity remained. No result was significant with the E4 allele. The E2 allele

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“…For the most part, genetic tests remain in the research phase and are not currently employed in clinical practice, the exception being apolipoprotein E (APOE) genotype analysis. APOE genotype does not have a major effect on PSP 53–55. More recently, an extended tau haplotype (H1 vs. H2) has been identified and studies have documented increased frequency of the H1 haplotype and H1/H1 genotype in PSP,56–59 suggesting that this genetic test may contribute eventually to differential diagnosis.…”

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confidence: 98%

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy Brain Bank

2003

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Diagnostic accuracy has been addressed previously for Parkinson's disease in a brain bank collection, but accuracy of progressive supranuclear palsy (PSP) has not been addressed in a similar setting. Clinical and genetic features of pathologically confirmed cases of PSP were compared with misdiagnosed cases to determine ways to improve diagnostic accuracy. Medical records were reviewed for 180 cases sent to the Society of Progressive Supranuclear Palsy Brain Bank that had standardized neuropathologic evaluations as well as determination of apolipoprotein E and tau genotypes. Of the 180 cases studied, 137 had PSP and 43 had other pathologic diagnoses. Corticobasal degeneration (CBD), multiple system atrophy (MSA), and diffuse Lewy body disease (DLBD) accounted for 70% of the misdiagnosed cases. History of tremor, psychosis, dementia, and asymmetric findings were more frequent in misdiagnosed cases. The frequency of H1 tau haplotype (93 vs. 80%) and H1H1 genotype (86 vs. 66%) were significantly greater and APOE epsilon4 carrier state was significantly less (17 vs. 41 %) in PSP compared with misdiagnosed cases. Pathologic evaluation of clinically diagnosed PSP remains important for definitive diagnosis, and CBD, MSA, and DLBD are the disorders most likely to be misdiagnosed as PSP. Tremor, psychosis, early dementia, asymmetric findings, absence of H1 haplotype, and presence of APOE epsilon4 should raise questions about a diagnosis of PSP.

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Normal distribution of apolipoprotein E alleles in progressive supranuclear palsy

Cited by 25 publications

References 8 publications

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy

Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis

Diagnostic accuracy of progressive supranuclear palsy in the Society for Progressive Supranuclear Palsy Brain Bank

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