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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},
}