Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Höhn, L; Hußler, W; Richter, A; Smalla, KH; Birkl-Toeglhofer, AM; Birkl, C; Vielhaber, S; Leber, SL; Gundelfinger, ED; Haybaeck, J; Schreiber, S; Seidenbecher, CI.
Extracellular Matrix Changes in Subcellular Brain Fractions and Cerebrospinal Fluid of Alzheimer's Disease Patients.
Int J Mol Sci. 2023; 24(6):
Doi: 10.3390/ijms24065532
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- Co-authors Med Uni Graz
- Birkl Christoph
- Birkl-Töglhofer Anna Maria
- Haybäck Johannes
- Leber Stefan
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Brevican - metabolism
- Aggrecans - metabolism
- Neurocan - cerebrospinal fluid
- Alzheimer Disease - metabolism
- Extracellular Matrix - metabolism
- Brain - metabolism
- tau Proteins - metabolism
- Amyloid beta-Peptides - metabolism
- Biomarkers - metabolism
- Find related publications in this database (Keywords)
- aggrecan
- brevican
- cerebrospinal fluid
- CSF
- HAPLN1
- neurocan
- tenascin-R