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Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias.
Mol Psychiatry 2007; 12(7):671-80MP

Abstract

Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-beta (Abeta) peptide patterns, using the quantitative Abeta-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on Abeta1-38. The main outcome measures were a striking decrease of Abeta1-42 in AD (P=7.4 x 10(-19)), and most interestingly a pronounced decrease of Abeta1-38 in FTD (P=9.6 x 10(-7)). Moreover, a novel peptide that most probably represents an oxidized alpha-helical form of Abeta1-40 (Abeta1-40(ox)) displayed a highly significant increase in DLB (P=3.7 x 10(-3)) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Abeta peptide abundances (Abeta1-X%) was clearly superior to absolute CSF Abeta levels. Abeta1-42% and Abeta1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. Abeta1-40(ox)% yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between Abeta1-38 levels as measured by the Abeta-SDS-PAGE/immunoblot and MSD, respectively. CSF Abeta peptides may reflect disease-specific impact of distinct neurodegenerative processes on Abeta peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB.

Authors+Show Affiliations

Department of Psychiatry, University of Goettingen, Goettingen, Germany. mbibl@gwdg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Validation Studies

Language

eng

PubMed ID

17339876

Citation

Bibl, M, et al. "Validation of Amyloid-beta Peptides in CSF Diagnosis of Neurodegenerative Dementias." Molecular Psychiatry, vol. 12, no. 7, 2007, pp. 671-80.
Bibl M, Mollenhauer B, Lewczuk P, et al. Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. Mol Psychiatry. 2007;12(7):671-80.
Bibl, M., Mollenhauer, B., Lewczuk, P., Esselmann, H., Wolf, S., Trenkwalder, C., ... Wiltfang, J. (2007). Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. Molecular Psychiatry, 12(7), pp. 671-80.
Bibl M, et al. Validation of Amyloid-beta Peptides in CSF Diagnosis of Neurodegenerative Dementias. Mol Psychiatry. 2007;12(7):671-80. PubMed PMID: 17339876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of amyloid-beta peptides in CSF diagnosis of neurodegenerative dementias. AU - Bibl,M, AU - Mollenhauer,B, AU - Lewczuk,P, AU - Esselmann,H, AU - Wolf,S, AU - Trenkwalder,C, AU - Otto,M, AU - Stiens,G, AU - Rüther,E, AU - Kornhuber,J, AU - Wiltfang,J, Y1 - 2007/03/06/ PY - 2007/3/7/pubmed PY - 2007/8/29/medline PY - 2007/3/7/entrez SP - 671 EP - 80 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 12 IS - 7 N2 - Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-beta (Abeta) peptide patterns, using the quantitative Abeta-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on Abeta1-38. The main outcome measures were a striking decrease of Abeta1-42 in AD (P=7.4 x 10(-19)), and most interestingly a pronounced decrease of Abeta1-38 in FTD (P=9.6 x 10(-7)). Moreover, a novel peptide that most probably represents an oxidized alpha-helical form of Abeta1-40 (Abeta1-40(ox)) displayed a highly significant increase in DLB (P=3.7 x 10(-3)) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Abeta peptide abundances (Abeta1-X%) was clearly superior to absolute CSF Abeta levels. Abeta1-42% and Abeta1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. Abeta1-40(ox)% yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between Abeta1-38 levels as measured by the Abeta-SDS-PAGE/immunoblot and MSD, respectively. CSF Abeta peptides may reflect disease-specific impact of distinct neurodegenerative processes on Abeta peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/17339876/Validation_of_amyloid_beta_peptides_in_CSF_diagnosis_of_neurodegenerative_dementias_ L2 - http://dx.doi.org/10.1038/sj.mp.4001967 DB - PRIME DP - Unbound Medicine ER -