The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study

Vefring, Hege K.; Haugarvoll, Kristoffer; Tysnes, Ole‐Bjørn; Larsen, Jan Petter; Kurz, Martin

doi:10.1111/j.1600-0404.2010.01362.x

Cited by 19 publications

(12 citation statements)

References 18 publications

(18 reference statements)

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“…However, these studies have yielded mixed results. While APOE polymorphism was not associated with PD in several studies [143, 241–248], others did find associations but differed in the terms of this association. Indeed, lower E4 allele frequency and higher E4 allele frequency were, respectively, associated in sporadic and familial PD with cognitive decline [249].…”

Section: Apoe and Other Neurodegenerative Diseasesmentioning

confidence: 98%

Function and Comorbidities of Apolipoprotein E in Alzheimer′s Disease

Leduc

Domenger

Beaumont

et al. 2011

International Journal of Alzheimer's Disease

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Alzheimer's disease (AD)—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE), the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

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Section: Apoe and Other Neurodegenerative Diseasesmentioning

confidence: 98%

Function and Comorbidities of Apolipoprotein E in Alzheimer′s Disease

Leduc

Domenger

Beaumont

et al. 2011

International Journal of Alzheimer's Disease

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“…Previous work has suggested ε4 as a risk factor for the age of onset, decline in cognitive impairment, and/or development of dementia in PD, ε2 has also been identified as a potential risk factor in PD, however this is at best a weak effect, and inconsistent across studies (Buchanan et al, 2007; Ezquerra et al, 2008; Gallegos-Arreola et al, 2009; Huang et al, 2006; Huang et al, 2004; Kurz et al, 2009; Lopez et al, 2007; Martinez et al, 2005; Pankratz et al, 2006; Ryu and Kwon, 2010; Vefring et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

A large study reveals no association between APOE and Parkinson's disease

Federoff

Jiménez-Rolando

Nalls

et al. 2012

Neurobiology of Disease

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Background Research focusing on the role of APOE in Parkinson’s disease (PD) has been largely inconclusive, creating a broad discrepancy in association studies. Objective To elucidate the role of APOE alleles in PD risk by studying a large sample size and controlling for population substructure. Patients and Methods In total, 3465 case and control samples were genotyped, obtained from the NINDS Neurogenetics repository. Results No significant differences in ε4 dosages exist between PD cases and controls. The frequency of ε4 carriers differed slightly between cases and controls at 24% (580/2412) and 26% (270/1053), respectively. Likewise, mean dosages of APOE ε2 were not significantly different between cases and controls. APOE ε2 carriers were observed at a frequency of 13.6% (329/2412) among cases and 15% (158/1053) among controls. Logistic regression models evaluating PD as possibly associated with ε4 or ε2 carrier status and allele dosages yielded no significant results. The mean MMSE score among all PD cases was 28.35 (SD = 2.58) and memory loss was reported in only 11.9% (105/879) of cases. Linear regression models comparing MMSE scores as predicted by ε4 or ε2 carrier status and allele dosages were not significant. Conclusions There is no association between APOE epsilon alleles and Parkinson’s disease.

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“…The greater severity of CAA in homozygous patients fits with this observation. It is unclear if APOE ε4 is associated with risk of PD or age of onset of PD [26,31,44,57,60]. On the other hand, there is more consistent evidence of an association between APOE ε4 and Alzheimer type pathology in PD [1,3,34,51].…”

Section: Discussionmentioning

confidence: 99%

Sequence variants in eukaryotic translation initiation factor 4-gamma (eIF4G1) are associated with Lewy body dementia

et al. 2012

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We recently reported a missense mutation and four variants in eukaryotic translation initiation factor 4-gamma (EIF4G1) associated with parkinsonism, dementia or both. In those with a positive family history, the mode of inheritance was autosomal dominant. Detailed neuropathologic descriptions of individuals with EIF4G1 genetic variants have not been reported. Herein, we report neuropathologic findings of three individuals from two American families with EIF4G1 variants. The patients had initial clinical presentations of dementia or parkinsonism and all had dementia at the time of autopsy. One family carried an EIF4G1 double variant, c.2056G>T (p.G686C) and c.3589C>T (p.R1197W), and one family carried variant c.1505C>T (p.A502V). All three patients also carried at least one ε4 allele of apolipoprotein E. One individual presented with cognitive impairment without significant parkinsonism; one presented with memory problems followed by bradykinesia; and the third presented with cardinal signs of Parkinson’s disease, followed more than a year later by cognitive dysfunction. Pathological examination showed diffuse cortical Lewy bodies and Lewy neurites in all patients. A small subset of Lewy bodies and Lewy neurites were immunopositive for eIF4G1. All patients had moderate to frequent non-neuritic, cortical amyloid plaques, mostly medial temporal neurofibrillary pathology (Braak neurofibrillary tangle stages of II to IV), and minimal or no TDP-43 pathology. The results suggest that in some patients variants in EIF4G1 can be associated with pathology that has a high likelihood of association with clinical features of dementia with Lewy bodies.

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The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study

Abstract: In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long-term follow-up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.

Cited by 19 publications

References 18 publications

Function and Comorbidities of Apolipoprotein E in Alzheimer′s Disease

Function and Comorbidities of Apolipoprotein E in Alzheimer′s Disease

A large study reveals no association between APOE and Parkinson's disease

Sequence variants in eukaryotic translation initiation factor 4-gamma (eIF4G1) are associated with Lewy body dementia

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