Journal Article

DZNE-2024-00934

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Assessing blood-brain barrier dysfunction and its association with Alzheimer's pathology, cognitive impairment and neuroinflammation.

Preis, L.Extern* ; Villringer, K. ; Brosseron, F.DZNE* ; Düzel, E.DZNE* ; Jessen, F.DZNE* ; Petzold, G. C.DZNE* ; Ramirez, A.DZNE* ; Spottke, A.DZNE* ; Fiebach, J. B. ; Peters, O. (Last author)DZNE*

2024
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s13195-024-01529-1

Abstract: Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability. However, the relationship between BBB dysfunction, cognitive impairment, and AD pathology remains unclear, with inconsistent findings in the literature.We conducted a cross-sectional study using data from the DELCODE and DESCRIBE cohorts to investigate BBB dysfunction in participants with normal cognition (NC), mild cognitive impairment (MCI), and AD dementia. BBB function was assessed using DCE-MRI and sPDGFRβ levels in cerebrospinal fluid and AD biomarkers Aβ and tau were measured. In a subset of patients, the CSF/plasma-ratio of albumin (QAlb) as a standard marker of BBB integrity and markers of neuroinflammation were analyzed.91 participants (NC: 44, MCI: 21, AD: 26) were included in the analysis. The average age was 74.4 years, 42% were female. Increased hippocampal BBB disruption was observed in the AD-group (Ktrans: 0.55 × 10- 3 min- 1 ± 0.74 × 10- 3 min- 1) but not the MCI-group (Ktrans: 0.177 × 10- 3 min- 1 ± 0.22 × 10- 3 min- 1), compared to the NC group (Ktrans: 0.19 × 10- 3 min- 1 ± 0.37 × 10- 3 min- 1, p < .01). sPDGFRβ was not significantly different between the cognitive groups. However, sPDGFRβ levels were significantly associated with age (r = .33, p < .01), independent of vascular risk factors. Further, sPDGFRβ showed significant positive associations with soluble Aβ levels (Aβ40: r = .57, p < .01; Aβ42: r = .39, p < .01) and YKL-40 (r = .53, p < .01), a marker of neuroinflammation. sPDGFRβ/DCE-MRI was not associated with overall AD biomarker positivity or APOE-status.In dementia, but not MCI, hippocampal BBB disruption was observed. sPDGFRβ increased with age and was associated with neuroinflammation independent of cognitive impairment. The association between Aβ and sPDGFRβ may indicate a bidirectional relationship reflecting pericytes' clearance of soluble Aβ and/or vasculotoxic properties of Aβ.

Keyword(s): Humans (MeSH) ; Blood-Brain Barrier: pathology (MeSH) ; Female (MeSH) ; Cognitive Dysfunction: diagnostic imaging (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Male (MeSH) ; Aged (MeSH) ; Alzheimer Disease: diagnostic imaging (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Cross-Sectional Studies (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Neuroinflammatory Diseases: diagnostic imaging (MeSH) ; Neuroinflammatory Diseases: pathology (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Biomarkers: blood (MeSH) ; Middle Aged (MeSH) ; Aged, 80 and over (MeSH) ; Receptor, Platelet-Derived Growth Factor beta: metabolism (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; tau Proteins: metabolism (MeSH) ; Alzheimer’s disease ; Alzheimer’s disease ; Blood-brain barrier ; DCE-MRI ; Mild cognitive impairment ; Pericyte ; sPDGFRβ ; Amyloid beta-Peptides ; Biomarkers ; Receptor, Platelet-Derived Growth Factor beta ; tau Proteins ; sPDGFRβ

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Contributing Institute(s):

1. Biomarker-Assisted Early Detection of Dementias (AG Peters)
2. Neuroinflammation, Biomarker (AG Heneka)
3. Clinical Neurophysiology and Memory (AG Düzel)
4. Clinical Alzheimer’s Disease Research (AG Jessen)
5. Vascular Neurology (AG Petzold)
6. Patient Studies (Bonn) (Patient Studies Bonn ; Patient Studies (Bonn))
7. Clinical Research Platform (CRP) (AG Spottke)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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