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@ARTICLE{Preis:271062,
author = {Preis, Lukas and Villringer, Kersten and Brosseron,
Frederic and Düzel, Emrah and Jessen, Frank and Petzold,
Gabor C and Ramirez, Alfredo and Spottke, Annika and
Fiebach, Jochen B and Peters, Oliver},
title = {{A}ssessing blood-brain barrier dysfunction and its
association with {A}lzheimer's pathology, cognitive
impairment and neuroinflammation.},
journal = {Alzheimer's research $\&$ therapy},
volume = {16},
number = {1},
issn = {1758-9193},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2024-00934},
pages = {172},
year = {2024},
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.},
keywords = {Humans / Blood-Brain Barrier: pathology / Female /
Cognitive Dysfunction: diagnostic imaging / Cognitive
Dysfunction: pathology / Male / Aged / Alzheimer Disease:
diagnostic imaging / Alzheimer Disease: pathology /
Cross-Sectional Studies / Magnetic Resonance Imaging /
Neuroinflammatory Diseases: diagnostic imaging /
Neuroinflammatory Diseases: pathology / Amyloid
beta-Peptides: cerebrospinal fluid / Amyloid beta-Peptides:
metabolism / Biomarkers: cerebrospinal fluid / Biomarkers:
blood / Middle Aged / Aged, 80 and over / Receptor,
Platelet-Derived Growth Factor beta: metabolism / tau
Proteins: cerebrospinal fluid / tau Proteins: metabolism /
Alzheimer’s disease (Other) / Alzheimer’s disease
(Other) / Blood-brain barrier (Other) / DCE-MRI (Other) /
Mild cognitive impairment (Other) / Pericyte (Other) /
sPDGFRβ (Other) / Amyloid beta-Peptides (NLM Chemicals) /
Biomarkers (NLM Chemicals) / Receptor, Platelet-Derived
Growth Factor beta (NLM Chemicals) / tau Proteins (NLM
Chemicals) / sPDGFRβ (Other)},
cin = {AG Peters / AG Heneka / AG Düzel / AG Jessen / AG Petzold
/ Patient Studies Bonn ; Patient Studies (Bonn) / AG
Spottke},
ddc = {610},
cid = {I:(DE-2719)5000000 / I:(DE-2719)1011303 /
I:(DE-2719)5000006 / I:(DE-2719)1011102 / I:(DE-2719)1013020
/ I:(DE-2719)1011101 / I:(DE-2719)1011103},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39085945},
pmc = {pmc:PMC11290219},
doi = {10.1186/s13195-024-01529-1},
url = {https://pub.dzne.de/record/271062},
}