β‐amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease

Wiltfang, Jens; Esselmann, Hermann; Smirnov, Alexandr; Bibl, Mirko; Cepek, Lukas; Steinacker, Petra; Mollenhauer, Brit; Büerger, Katharina; Hampel, Harald; Paul, Sabine; Neumann, Manuela; Maler, Manuel; Zerr, Inga; Kornhuber, Johannes; Kretzschmar, Hans A.; Poser, S.; Otto, Markus

doi:10.1002/ana.10661

Cited by 79 publications

(67 citation statements)

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“…First, this may be due to disease-specific interactions of each ongoing neurodegenerative dementia process with APP metabolism, which cannot be adequately represented by the sole measurement of absolute Aβ1–42 levels (Wiltfang et al ., 2001). Second, the percentage abundance of each Aβ peptide species displayed a lower inter-individual variance of values than its absolute levels (Wiltfang et al ., 2003). This corresponds to the observation that the abundances of single Aβ peptide species are closely correlated to each other and regulated in narrow limits, whereas the total amount of Aβ peptides varies inter-individually (Wiltfang et al ., 2002, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Second, the percentage abundance of each Aβ peptide species displayed a lower inter-individual variance of values than its absolute levels (Wiltfang et al ., 2003). This corresponds to the observation that the abundances of single Aβ peptide species are closely correlated to each other and regulated in narrow limits, whereas the total amount of Aβ peptides varies inter-individually (Wiltfang et al ., 2002, 2003). The ratio of the differentially altered Aβ1–42 to the Aβ1–37 levels enabled the best test accuracies and a highly significant differentiation of all diagnostic groups from each other, with the exception of DLB versus PDD.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased levels of CSF Aβ1–42 have been reported for patients with Alzheimer's disease (Motter et al ., 1995; Andreasen et al ., 2001, 2003; Wiltfang et al ., 2002, 2003; Mollenhauer et al ., 2005) and DLB (Andreasen et al ., 2001; Mollenhauer et al ., 2005). The reduction of Aβ1–42 levels in Alzheimer's disease has been explained by an increased clearance of the peptide from CSF into senile amyloid plaques for a long time (Motter et al ., 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The reduction of Aβ1–42 levels in Alzheimer's disease has been explained by an increased clearance of the peptide from CSF into senile amyloid plaques for a long time (Motter et al ., 1995). Other studies indicate the existence of alternative mechanisms, including the formation of SDS-stable oligomers (Podlisny et al ., 1995) and chaperone complexes of Aβ peptides with specific carrier proteins (Wiltfang et al ., 2002, 2003; Bibl et al ., 2004). However, misfolding and subsequent deposition of proteins is considered to be a major pathological event in both neurodegenerative diseases and amyloid pathology has also been reported for DLB (Merdes et al ., 2003).…”

Section: Discussionmentioning

confidence: 99%

“…This Aβ peptide pattern displayed disease-specific variations in its absolute and relative quantities in the CSF of patients with Alzheimer's disease, Creutzfeldt–Jakob disease (CJD), chronic inflammatory diseases and other neuropsychiatric diseases (Wiltfang et al ., 2002, 2003). …”

Section: Introductionmentioning

confidence: 99%

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

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

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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: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

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186

146

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Plasma and cerebrospinal fluid ABeta42 for the differential diagnosis of Alzheimer's disease dementia in participants diagnosed with any dementia subtype in a specialist care setting

Kokkinou

Beishon

Smailagic

et al. 2021

Cochrane Database of Systematic Reviews

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Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer's disease pathology better than Aβ42 in rapidly progressive dementias

Baiardi

Abu‐Rumeileh

Rossi

et al. 2018

Ann Clin Transl Neurol

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Objective Despite the critical importance of pathologically confirmed samples for biomarker validation, only a few studies have correlated CSF A β 42 values in vivo with postmortem Alzheimer's disease ( AD ) pathology, while none evaluated the CSF A β 42/A β 40 ratio. We compared CSF A β 42 and A β 42/A β 40 ratio as biomarkers predicting AD neuropathological changes in patients with a short interval between lumbar puncture and death. Methods We measured CSF A β 40 and A β 42 and assessed AD pathology in 211 subjects with rapidly progressive dementia ( RPD ) and a definite postmortem diagnosis of Creutzfeldt‐Jakob disease ( n = 159), AD ( n = 12), dementia with Lewy bodies ( DLB , n = 4), AD / DLB mixed pathologies ( n = 5), and various other pathologies ( n = 31). Results The score reflecting the severity of A β pathology showed a better correlation with ln(A β 42/A β 40) ( R 2 = 0.506, β = −0.713, P < 0.001) than with ln(A β 42) ( R 2 = 0.206, β = −0.458, P < 0.001), which was confirmed after adjusting for covariates. A β 42/A β 40 ratio showed significantly higher accuracy than A β 42 in the distinction between cases with or without AD pathology ( AUC 0.818 ± 0.028 vs. 0.643 ± 0.039), especially in patients with A β 42 levels ≤495 pg/mL ( AUC 0.888 ± 0.032 vs. 0.518 ± 0.064). Using a cut‐off value of 0.810, the analysis of A β 42/A β 40 ratio yielded 87.0% sensitivity, 88.2% specificity in the distinction between cases with an intermediate‐high level of AD pathology and those with low level or no AD pathology. Interpretation The present data support the use of CSF A β 42/A ...

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β‐amyloid peptides in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease

Cited by 79 publications

References 20 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

Plasma and cerebrospinal fluid ABeta42 for the differential diagnosis of Alzheimer's disease dementia in participants diagnosed with any dementia subtype in a specialist care setting

Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer's disease pathology better than Aβ42 in rapidly progressive dementias

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