Lack of association of APOE and tau polymorphisms with dementia in Parkinson’s disease

Ezquerra, Mario; Campdelacreu, Jaume; Gaig, Carles; Compta, Yaroslau; Muñoz, Esteban; Martı́, Marı́a José; Valldeoriola, Francesc; Tolosa, Eduardo

doi:10.1016/j.neulet.2008.10.018

Cited by 56 publications

(48 citation statements)

References 35 publications

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“…Consistent with our data, Mata and colleagues' recent study noted the detrimental effect of APOE ε4 on cognition in PD, and no effect for MAPT H1/H1 [9]. Also, a previous study of PD in Spain discarded a relationship between MAPT H1/H1 and dementia [28]. On the other hand, a recent 10-year follow-up for the CamPaIGN cohort found a link between MAPT H1/H1 and dementia, and no link for APOE ε4 [11].…”

Section: Discussionsupporting

confidence: 91%

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease

et al. 2017

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The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study’s objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients. The degree of dopaminergic depletion was investigated with [123I]FP-CIT SPECTs and the presence of dementia was ascertained with a long-term review based on established criteria. The association between genetic and imaging parameters was studied with linear regression, and the relationship with dementia onset with Cox regression. We found that APOE2 allele (Pput = 0.002; Pcau = 0.01), the minor allele 'G' in SNCA polymorphism (Pput = 0.02; Pcau = 0.006) and GBA deleterious variants in (Pput = 0.01; Pcau = 0.001) had a detrimental effect on striatal [123I]FP-CIT uptake in PD. Conversely, Met/Met carriers in COMT polymorphism had increased caudate uptake (Pcau = 0.03). The development of dementia was influenced by APOE4 allele (HR = 1.90; P = 0.03) and GBA deleterious variants (HR = 2.44; P = 0.01). Finally, we observed no role of MAPT locus in any of the syndromes. As a conclusion, APOE2, SNCA, COMT and GBA influence frontostriatal dysfunction whereas APOE4 and GBA influence the development of dementia, suggesting a double-edged role of GBA. The dichotomy of the dual syndromes may be driven by a broad dichotomy in these genetic factors.

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Section: Discussionsupporting

confidence: 91%

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease

et al. 2017

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“…A second cross-sectional study in Spain found no difference in H1 frequency between demented (n = 86) and non-demented (n = 138) PD patients. 40 In our much larger cohort we did not observe an association between MAPT H1 and baseline performance on any cognitive tests, and none of the variables examined even approached significance (Table 3). Because of the substantial differences in methodologies employed, caution must be used in comparing our findings with those of previous studies.…”

Section: Discussionmentioning

confidence: 60%

APOE,MAPT, andSNCAGenes and Cognitive Performance in Parkinson Disease

et al. 2014

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“…Here we show that H1 carrier patients were less accurate with difficult spatial rotations, and sustained less activity in the parietal cortex and caudate nuclei (Williams-Gray et al , 2009 a ), essential areas for spatial rotations (Harris et al , 2000). Others have argued that there is no relationship between MAPT haplotype and visuospatial performance (Goldberg and Weinberger, 2004; Ezquerra et al , 2008; Rowe et al , 2008; Morley et al , 2012), which was the case here for easy items. Our hypothesis is that as Parkinson’s disease progresses, the difference between H1 and H2 haplotype will emerge but initially only for more difficult visuospatial tasks.…”

Section: Discussionmentioning

confidence: 64%

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

Nombela

Rowe

Winder‐Rhodes

et al. 2014

Brain

136

134

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See Dujardin (doi:) for a scientific commentary on this article. Nombela et al. present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.

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Lack of association of APOE and tau polymorphisms with dementia in Parkinson’s disease

Cited by 56 publications

References 35 publications

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease

APOE,MAPT, andSNCAGenes and Cognitive Performance in Parkinson Disease

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

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