The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.

Gibb, W. R. G.; Lees, Andrew J.

doi:10.1136/jnnp.51.6.745

Cited by 3,019 publications

(1,884 citation statements)

References 27 publications

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“…All 21 patients (16 men and 5 women) of this group fulfilled the DSM IV criteria for dementia and the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for idiopathic Parkinson's disease (Gibb and Lees, 1988). All patients in this group presented parkinsonism at least one year before onset of dementia according to the criteria of McKeith et al .…”

Section: Methodsmentioning

confidence: 99%

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

180

144

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As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Aβ) peptides, such as Aβ1–42. Absolute Aβ1–42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Aβ-sodium-dodecylsulphate–polyacrylamide-gel-electrophoresis with Western immunoblot (Aβ-SDS–PAGE/immunoblot) revealed a highly conserved Aβ peptide pattern of the carboxy-terminally truncated Aβ peptides 1–37, 1–38, 1–39 in addition to 1–40 and 1–42 in human CSF. We used the Aβ-SDS–PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Aβ peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Aβ peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases—Alzheimer's disease, DLB and PDD. The Aβ peptide patterns displayed disease-specific variations and the ratio of the differentially altered Aβ1–42 to the Aβ1–37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Aβ-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized α-helical form of Aβ1–40 (Aβ1–40*). The increased abundance of Aβ1–40* probably reflects a disease-specific alteration of the Aβ1–40 metabolism in DLB. We conclude that Aβ peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Aβ peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

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Section: Methodsmentioning

confidence: 99%

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

180

144

View full text Add to dashboard Cite

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“…Calne et al [7] added the category clinically definite idiopathic parkinsonism, which required three of the four cardinal symptoms originally listed [4] or alternatively, two of these, with one displaying asymmetry. The UK Brain Bank criteria [2] suggested the diagnosis of parkinsonian syndrome be assigned when bradykinesia is present, plus at least one of rigidity, rest tremor and postural instability. A large number of exclusion criteria also were listed (notably, history of repeated strokes indicating atherosclerotic parkinsonism and severe autonomic involvement indicating the diagnosis of multiple system atrophy -MSA); as supportive criteria, progressive disorder and l-dopa response were added.…”

Section: Diagnosis Of Pdmentioning

confidence: 99%

“…Among 100 cases with clinically diagnosed PD, 76 fulfilled pathological criteria for PD, whilst 24 were misdiagnosed [11]. When the UK Brain Bank diagnostic criteria [2] were retrospectively applied, diagnostic accuracy increased to 82%. Asymmetrical onset, no atypical clinical features and no other cause of parkinsonian syndrome were the best predictors of histopathological confirmation of PD [12].…”

Section: Diagnosis Of Pdmentioning

confidence: 99%

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Epidemiology and etiology of Parkinson’s disease: a review of the evidence

et al. 2011

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“…PD is characterized clinically by resting tremor, rigidity, bradykinesia, and postural instability (Calne, 2005;Hughes et al, 2001). The pathological characteristics of this disease are a progressive loss of dopaminergic neurons, primarily in the substantia nigra pars compacta, and the presence of eosinophilic cytoplasmic inclusions, called Lewy bodies, throughout the brain (Braak et al, 2003;Gibb and Lees, 1988;Jellinger, 2001). …”

Section: Introductionmentioning

confidence: 99%

Sepiapterin reductase expression is increased in Parkinson's disease brain tissue

et al. 2007

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The PARK3 locus on chromosome 2p13 has shown linkage to both the development and age of onset of Parkinson's disease (PD). One candidate gene at this locus is sepiapterin reductase (SPR). Sepiapterin reductase catalyzes the final step in the biosynthetic pathway of tetrahydrobiopterin (BH 4 ), an essential cofactor for aromatic amino acid hydrolases including tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. The expression of SPR was assayed using semiquantitative real-time RT-PCR in human post-mortem cerebellar tissue from neuropathologically confirmed PD cases and neurologically normal controls. The expression of other enzymes involved in BH 4 biosynthesis, including aldose reductase (AKR1B1), carbonyl reductase (CBR1 and CBR3), GTP-cyclohydrolase I (GCH1), and 6-pyruvoyltetrahydrobiopterin (PTS), was also examined. Single-nucleotide polymorphisms around the SPR gene that have been previously reported to show association to PD affection and onset age were genotyped in these samples. Expression of SPR showed a significant 4-fold increase in PD cases relative to controls, while the expression of AKR1B1 and PTS was significantly decreased in PD cases. No difference in expression was detected for CBR1, CBR3, and GCH1. Genetic variants did not show a significant effect on SPR expression, however, this is likely due to the low frequency of rare genotypes in the sample. While the association of SPR to PD is not strong enough to support that this is the PARK3 gene, this study further implicates a role for SPR in idiopathic PD.

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The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.

Cited by 3,019 publications

References 27 publications

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

Sepiapterin reductase expression is increased in Parkinson's disease brain tissue

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