Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients
The brain’s extracellular matrix (ECM) is assumed to undergo rearrangements in Alzheimer’s disease (AD). Here, we investigated changes of key components of the hyaluronan-based ECM in independent samples of post-mortem brains (N = 19), cerebrospinal fluids (CSF; N = 70), and RNAseq data (N = 107; fr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5532 |
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| author | Lukas Höhn Wilhelm Hußler Anni Richter Karl-Heinz Smalla Anna-Maria Birkl-Toeglhofer Christoph Birkl Stefan Vielhaber Stefan L. Leber Eckart D. Gundelfinger Johannes Haybaeck Stefanie Schreiber Constanze I. Seidenbecher |
| author_facet | Lukas Höhn Wilhelm Hußler Anni Richter Karl-Heinz Smalla Anna-Maria Birkl-Toeglhofer Christoph Birkl Stefan Vielhaber Stefan L. Leber Eckart D. Gundelfinger Johannes Haybaeck Stefanie Schreiber Constanze I. Seidenbecher |
| author_sort | Lukas Höhn |
| collection | DOAJ |
| description | The brain’s extracellular matrix (ECM) is assumed to undergo rearrangements in Alzheimer’s disease (AD). Here, we investigated changes of key components of the hyaluronan-based ECM in independent samples of post-mortem brains (N = 19), cerebrospinal fluids (CSF; N = 70), and RNAseq data (N = 107; from The Aging, Dementia and TBI Study) of AD patients and non-demented controls. Group comparisons and correlation analyses of major ECM components in soluble and synaptosomal fractions from frontal, temporal cortex, and hippocampus of control, low-grade, and high-grade AD brains revealed a reduction in brevican in temporal cortex soluble and frontal cortex synaptosomal fractions in AD. In contrast, neurocan, aggrecan and the link protein HAPLN1 were up-regulated in soluble cortical fractions. In comparison, RNAseq data showed no correlation between aggrecan and brevican expression levels and Braak or CERAD stages, but for hippocampal expression of HAPLN1, neurocan and the brevican-interaction partner tenascin-R negative correlations with Braak stages were detected. CSF levels of brevican and neurocan in patients positively correlated with age, total tau, p-Tau, neurofilament-L and Aβ1-40. Negative correlations were detected with the Aβ ratio and the IgG index. Altogether, our study reveals spatially segregated molecular rearrangements of the ECM in AD brains at RNA or protein levels, which may contribute to the pathogenic process. |
| first_indexed | 2024-03-11T06:26:04Z |
| format | Article |
| id | doaj.art-637f047ad44b44fc84f400ce1b94e765 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:26:04Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-637f047ad44b44fc84f400ce1b94e7652023-11-17T11:35:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246553210.3390/ijms24065532Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease PatientsLukas Höhn0Wilhelm Hußler1Anni Richter2Karl-Heinz Smalla3Anna-Maria Birkl-Toeglhofer4Christoph Birkl5Stefan Vielhaber6Stefan L. Leber7Eckart D. Gundelfinger8Johannes Haybaeck9Stefanie Schreiber10Constanze I. Seidenbecher11Leibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyLeibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyLeibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyLeibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Neuroradiology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Neurology, Otto-von-Guericke University, 39120 Magdeburg, GermanyDivision of Neuroradiology, Vascular and Interventional Radiology, Medical University of Graz, 8036 Graz, AustriaLeibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, AustriaDepartment of Neurology, Otto-von-Guericke University, 39120 Magdeburg, GermanyLeibniz Institute for Neurobiology (LIN), 39118 Magdeburg, GermanyThe brain’s extracellular matrix (ECM) is assumed to undergo rearrangements in Alzheimer’s disease (AD). Here, we investigated changes of key components of the hyaluronan-based ECM in independent samples of post-mortem brains (N = 19), cerebrospinal fluids (CSF; N = 70), and RNAseq data (N = 107; from The Aging, Dementia and TBI Study) of AD patients and non-demented controls. Group comparisons and correlation analyses of major ECM components in soluble and synaptosomal fractions from frontal, temporal cortex, and hippocampus of control, low-grade, and high-grade AD brains revealed a reduction in brevican in temporal cortex soluble and frontal cortex synaptosomal fractions in AD. In contrast, neurocan, aggrecan and the link protein HAPLN1 were up-regulated in soluble cortical fractions. In comparison, RNAseq data showed no correlation between aggrecan and brevican expression levels and Braak or CERAD stages, but for hippocampal expression of HAPLN1, neurocan and the brevican-interaction partner tenascin-R negative correlations with Braak stages were detected. CSF levels of brevican and neurocan in patients positively correlated with age, total tau, p-Tau, neurofilament-L and Aβ1-40. Negative correlations were detected with the Aβ ratio and the IgG index. Altogether, our study reveals spatially segregated molecular rearrangements of the ECM in AD brains at RNA or protein levels, which may contribute to the pathogenic process.https://www.mdpi.com/1422-0067/24/6/5532aggrecanbrevicancerebrospinal fluid/CSFHAPLN1neurocantenascin-R |
| spellingShingle | Lukas Höhn Wilhelm Hußler Anni Richter Karl-Heinz Smalla Anna-Maria Birkl-Toeglhofer Christoph Birkl Stefan Vielhaber Stefan L. Leber Eckart D. Gundelfinger Johannes Haybaeck Stefanie Schreiber Constanze I. Seidenbecher Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients International Journal of Molecular Sciences aggrecan brevican cerebrospinal fluid/CSF HAPLN1 neurocan tenascin-R |
| title | Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients |
| title_full | Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients |
| title_fullStr | Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients |
| title_full_unstemmed | Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients |
| title_short | Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer’s Disease Patients |
| title_sort | extracellular matrix changes in subcellular brain fractions and cerebrospinal fluid of alzheimer s disease patients |
| topic | aggrecan brevican cerebrospinal fluid/CSF HAPLN1 neurocan tenascin-R |
| url | https://www.mdpi.com/1422-0067/24/6/5532 |
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