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Sabri, Osama [Author]; Meyer, Philipp M [Author]; Hoepping, Alexander [Author]; Smits, Rene [Author]; Franke, Annegret [Author]; Sattler, Bernhard [Author]; Tiepolt, Solveig [Author]; Fischer, Steffen [Author]; Deuther-Conrad, Winnie [Author]; Hegerl, Ulrich [Author]; Barthel, Henryk [Author]; Schönknecht, Peter [Author]; Gräf, Susanne [Author]; Brust, Peter [Author]; Hesse, Swen [Author]; Wilke, Stephan [Author]; Becker, Georg-Alexander [Author]; Rullmann, Michael [Author]; Patt, Marianne [Author]; Luthardt, Julia [Author]; Wagenknecht, Gudrun [Author]

Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer’s dementia

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  • Media type: E-Article
  • Title: Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer’s dementia
  • Contributor: Sabri, Osama [Author]; Meyer, Philipp M [Author]; Hoepping, Alexander [Author]; Smits, Rene [Author]; Franke, Annegret [Author]; Sattler, Bernhard [Author]; Tiepolt, Solveig [Author]; Fischer, Steffen [Author]; Deuther-Conrad, Winnie [Author]; Hegerl, Ulrich [Author]; Barthel, Henryk [Author]; Schönknecht, Peter [Author]; Gräf, Susanne [Author]; Brust, Peter [Author]; Hesse, Swen [Author]; Wilke, Stephan [Author]; Becker, Georg-Alexander [Author]; Rullmann, Michael [Author]; Patt, Marianne [Author]; Luthardt, Julia [Author]; Wagenknecht, Gudrun [Author]
  • imprint: Oxford Univ. Press, 2018
  • Published in: Brain 141(6), 1840 - 1854 (2018). doi:10.1093/brain/awy099
  • Language: English
  • DOI: https://doi.org/10.1093/brain/awy099
  • ISSN: 1460-2156; 0006-8950
  • Origination:
  • Footnote: Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen.
  • Description: In early Alzheimer’s dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer’s dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer’s dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (−)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer’s dementia. Fourteen non-smoking patients with mild Alzheimer’s dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (−)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer’s dementia compared to healthy controls, there was significantly lower VT, especially within the ...
  • Access State: Open Access