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000271062 1001_ $$0P:(DE-2719)9000703$$aPreis, Lukas$$b0$$udzne
000271062 245__ $$aAssessing blood-brain barrier dysfunction and its association with Alzheimer's pathology, cognitive impairment and neuroinflammation.
000271062 260__ $$aLondon$$bBioMed Central$$c2024
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000271062 520__ $$aBlood-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.
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000271062 650_2 $$2MeSH$$aHumans
000271062 650_2 $$2MeSH$$aBlood-Brain Barrier: pathology
000271062 650_2 $$2MeSH$$aFemale
000271062 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000271062 650_2 $$2MeSH$$aCognitive Dysfunction: pathology
000271062 650_2 $$2MeSH$$aMale
000271062 650_2 $$2MeSH$$aAged
000271062 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000271062 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000271062 650_2 $$2MeSH$$aCross-Sectional Studies
000271062 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000271062 650_2 $$2MeSH$$aNeuroinflammatory Diseases: diagnostic imaging
000271062 650_2 $$2MeSH$$aNeuroinflammatory Diseases: pathology
000271062 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000271062 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000271062 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000271062 650_2 $$2MeSH$$aBiomarkers: blood
000271062 650_2 $$2MeSH$$aMiddle Aged
000271062 650_2 $$2MeSH$$aAged, 80 and over
000271062 650_2 $$2MeSH$$aReceptor, Platelet-Derived Growth Factor beta: metabolism
000271062 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000271062 650_2 $$2MeSH$$atau Proteins: metabolism
000271062 650_7 $$2Other$$aAlzheimer’s disease
000271062 650_7 $$2Other$$aAlzheimer’s disease
000271062 650_7 $$2Other$$aBlood-brain barrier
000271062 650_7 $$2Other$$aDCE-MRI
000271062 650_7 $$2Other$$aMild cognitive impairment
000271062 650_7 $$2Other$$aPericyte
000271062 650_7 $$2Other$$asPDGFRβ
000271062 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000271062 650_7 $$2NLM Chemicals$$aBiomarkers
000271062 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, Platelet-Derived Growth Factor beta
000271062 650_7 $$2NLM Chemicals$$atau Proteins
000271062 650_7 $$2Other$$asPDGFRβ
000271062 7001_ $$aVillringer, Kersten$$b1
000271062 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b2$$udzne
000271062 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b3$$udzne
000271062 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b4$$udzne
000271062 7001_ $$0P:(DE-2719)2810273$$aPetzold, Gabor C$$b5$$udzne
000271062 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b6$$udzne
000271062 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b7$$udzne
000271062 7001_ $$aFiebach, Jochen B$$b8
000271062 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b9$$eLast author$$udzne
000271062 773__ $$0PERI:(DE-600)2506521-X$$a10.1186/s13195-024-01529-1$$gVol. 16, no. 1, p. 172$$n1$$p172$$tAlzheimer's research & therapy$$v16$$x1758-9193$$y2024
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