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Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease.
J Alzheimers Dis 2014; 42(1):157-67JA

Abstract

BACKGROUND

Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear.

OBJECTIVE

To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions.

METHODS

We measured markers of amyloid-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses: subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers.

RESULTS

CSF levels of sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD.

CONCLUSIONS

CSF biomarkers of AβPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions.

Authors+Show Affiliations

Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.Memory Unit, Department of Neurology, Inst. Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en enfermedades Neurodegenerativas, CIBERNED, Spain.

Pub Type(s)

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

Language

eng

PubMed ID

24820015

Citation

Alcolea, Daniel, et al. "Relationship Between β-Secretase, Inflammation and Core Cerebrospinal Fluid Biomarkers for Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 42, no. 1, 2014, pp. 157-67.
Alcolea D, Carmona-Iragui M, Suárez-Calvet M, et al. Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease. J Alzheimers Dis. 2014;42(1):157-67.
Alcolea, D., Carmona-Iragui, M., Suárez-Calvet, M., Sánchez-Saudinós, M. B., Sala, I., Antón-Aguirre, S., ... Lleó, A. (2014). Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 42(1), pp. 157-67. doi:10.3233/JAD-140240.
Alcolea D, et al. Relationship Between β-Secretase, Inflammation and Core Cerebrospinal Fluid Biomarkers for Alzheimer's Disease. J Alzheimers Dis. 2014;42(1):157-67. PubMed PMID: 24820015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease. AU - Alcolea,Daniel, AU - Carmona-Iragui,María, AU - Suárez-Calvet,Marc, AU - Sánchez-Saudinós,M Belén, AU - Sala,Isabel, AU - Antón-Aguirre,Sofía, AU - Blesa,Rafael, AU - Clarimón,Jordi, AU - Fortea,Juan, AU - Lleó,Alberto, PY - 2014/5/14/entrez PY - 2014/5/14/pubmed PY - 2015/5/12/medline KW - Alzheimer's disease KW - YKL-40 KW - amyloid-β protein precursor KW - biological markers KW - cerebrospinal fluid KW - frontotemporal dementia KW - inflammation KW - β-secretase SP - 157 EP - 67 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 42 IS - 1 N2 - BACKGROUND: Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear. OBJECTIVE: To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions. METHODS: We measured markers of amyloid-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses: subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers. RESULTS: CSF levels of sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD. CONCLUSIONS: CSF biomarkers of AβPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24820015/Relationship_between_β_Secretase_inflammation_and_core_cerebrospinal_fluid_biomarkers_for_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-140240 DB - PRIME DP - Unbound Medicine ER -