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

Singleton, Andrew B.; Wharton, Anna; O’Brien, Kirsty; Walker, Matthew P.; McKeith, Ian G.; Ballard, Clive; O’Brien, John; Perry, Robert H.; Ince, Paul G.; Edwardson, James A.; Morris, Christopher M.

doi:10.1159/000066022

Cited by 60 publications

(39 citation statements)

References 30 publications

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“…This fi nding is consistent with several other studies which also found no difference in the 4 allele frequency between AD and DLB [34][35][36] . In addition, the frequency of atrophic changes seen on CT scans was not different between the two groups.…”

Section: Discussionsupporting

confidence: 93%

The Alzheimer Variant of Lewy Body Disease: A Pathologically Confirmed Case-Control Study

Perneczky

Mösch²,

Neumann³

et al. 2005

Dement Geriatr Cogn Disord

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The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer’s disease (AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein ε4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD.

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Section: Discussionsupporting

confidence: 93%

The Alzheimer Variant of Lewy Body Disease: A Pathologically Confirmed Case-Control Study

Perneczky

Mösch²,

Neumann³

et al. 2005

Dement Geriatr Cogn Disord

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“…For instance, the apolipoprotein-E ε4 (APOE ε4) gene is the most consistently associated genetic risk factor for AD [69][70][71]. The APOE gene has three major isoforms -ε2, ε3 and ε4, which differ from one another only by a single amino acid residue.…”

Section: Interactions Between Buche and Other Ad Susceptibility Genesmentioning

confidence: 99%

Cholinesterases: Roles in the Brain During Health and Disease

Ballard

Greig²,

Guillozet-Bongaarts³

et al. 2005

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325

190

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The cholinergic hypothesis of decline in dementia, whereby deficits in learning, memory and behavior are caused, at least in part, by decreased levels of acetylcholine (ACh) in the brain, first emerged more than 20 years ago. The role for acetylcholinesterase (AChE) and its inhibition in this scheme has long been accepted, but findings from preclinical experiments and clinical trials have placed butyrylcholinesterase (BuChE) alongside AChE as an important contributor to the occurrence, symptoms, progression and responses to treatment in dementia. A number of new lines of evidence suggest that both cholinesterase inhibitors (ChEs) may have broader functions in the CNS than previously thought, which relate to both 'classical' esterase activities of the enzymes as well as non-classical actions unrelated to their enzymatic function. Data suggest involvement of the ChEs in modulating glial activation, cerebral blood flow, the amyloid cascade, and tau phosphorylation. It has therefore been speculated that some actions of the ChEs could affect the underlying disease processes in Alzheimer's disease (AD), and that pharmacological manipulation with ChE inhibitors may affect long-term disease progression. Focusing on new findings relating to BuChE, we review recent evidence that has extended knowledge into the roles of ChEs in health, disease and aging.

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“…Findings regarding APOE polymorphisms in DLB have so far been inconclusive. Some studies show evidence for more frequent occurrence of e4 alleles in DLB compared to normal controls but similar to AD, indicating that DLB shares the APOE 4 allele with AD as a common risk factor, although there may be some differences in the way the e4 allele affects the phenotypic expression of disease [42,43] . Others studies, however, have been unable to reproduce this finding and have shown a similar proportion of APOE 4 in DLB and controls [44] , including a recent study with pathologic confirmation of the diagnosis [20] .…”

Section: Genetic Testingmentioning

confidence: 99%

Early Discriminatory Diagnosis of Dementia with Lewy Bodies

Aarsland

Kurz

Beyer

et al. 2008

Dement Geriatr Cogn Disord

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Background: The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer’s disease (AD). Method: We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. Results: The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid β (aβ) isoforms as well as α-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. Conclusion: Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

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

Cited by 60 publications

References 30 publications

The Alzheimer Variant of Lewy Body Disease: A Pathologically Confirmed Case-Control Study

The Alzheimer Variant of Lewy Body Disease: A Pathologically Confirmed Case-Control Study

Cholinesterases: Roles in the Brain During Health and Disease

Early Discriminatory Diagnosis of Dementia with Lewy Bodies

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