Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer's disease: a voxel-based lesion mapping study

Katrin Morgen; Michael Schneider; Lutz Frölich; Heike Tost; Michael M Plichta; Heike Kölsch; Fabian Rakebrandt; Otto Rienhoff; Frank Jessen; Oliver Peters; Holger Jahn; Christian Luckhaus; Michael Hüll; Hermann-Josef Gertz; Johannes Schröder; Harald Hampel; Stefan J Teipel; Johannes Pantel; Isabella Heuser; Jens Wiltfang; Eckart Rüther; Johannes Kornhuber; Wolfgang Maier; Andreas Meyer-Lindenberg

doi:10.1186/s13195-015-0111-8

Apolipoprotein E-dependent load of white matter hyperintensities in Alzheimer's disease: a voxel-based lesion mapping study

Alzheimers Res Ther. 2015 May 15;7(1):27. doi: 10.1186/s13195-015-0111-8. eCollection 2015.

Authors

Katrin Morgen¹, Michael Schneider², Lutz Frölich², Heike Tost², Michael M Plichta², Heike Kölsch³, Fabian Rakebrandt⁴, Otto Rienhoff⁴, Frank Jessen⁵, Oliver Peters⁶, Holger Jahn⁷, Christian Luckhaus⁸, Michael Hüll⁹, Hermann-Josef Gertz¹⁰, Johannes Schröder¹¹, Harald Hampel¹², Stefan J Teipel¹³, Johannes Pantel¹⁴, Isabella Heuser⁶, Jens Wiltfang¹⁵, Eckart Rüther¹⁶, Johannes Kornhuber¹⁷, Wolfgang Maier⁵, Andreas Meyer-Lindenberg²

Affiliations

¹ Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany ; AHG-Klinik für Psychosomatik, Kurbrunnenstr. 12, 67098, Bad Dürkheim, Germany.
² Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.
³ Institute of Human Genetics, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
⁴ Department of Medical Informatics, University of Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
⁵ Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Holbeinstr. 13-15, 53175, Bonn, Germany.
⁶ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Germany.
⁷ Department of Psychiatry and Psychotherapy, University of Hamburg, Martinistr. 52, 20246, Hamburg, Germany.
⁸ Department of Psychiatry and Psychotherapy, University of Düsseldorf, Bergische Landstr. 2, 40629, Düsseldorf, Germany.
⁹ Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstr. 5 79104, Freiburg, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, University of Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany.
¹¹ Department of Psychiatry and Psychotherapy, University of Heidelberg, Voßstr. 5, 69115, Heidelberg, Germany.
¹² Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital de la Salpêtrière Paris, Université Pierre et Marie Curie, 47 Blvd. de lHopital, 75013, Paris, France.
¹³ Department of Psychiatry and Psychotherapy, University of Rostock and DZNE Rostock, Gehlsheimerstr. 20, 18147 Rostock, Rostock, Germany.
¹⁴ Institute of General Practice, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
¹⁵ Department of Psychiatry and Psychotherapy, University of Essen, Virchowstr. 174, 45147, Essen, Germany.
¹⁶ Department of Psychiatry and Psychotherapy, University of Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany.
¹⁷ Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.

Abstract

Introduction: White matter (WM) magnetic resonance imaging (MRI) hyperintensities are common in Alzheimer's disease (AD), but their pathophysiological relevance and relationship to genetic factors are unclear. In the present study, we investigated potential apolipoprotein E (APOE)-dependent effects on the extent and cognitive impact of WM hyperintensities in patients with AD.

Methods: WM hyperintensity volume on fluid-attenuated inversion recovery images of 201 patients with AD (128 carriers and 73 non-carriers of the APOE ε4 risk allele) was determined globally as well as regionally with voxel-based lesion mapping. Clinical, neuropsychological and MRI data were collected from prospective multicenter trials conducted by the German Dementia Competence Network.

Results: WM hyperintensity volume was significantly greater in non-carriers of the APOE ε4 allele. Lesion distribution was similar among ε4 carriers and non-carriers. Only ε4 non-carriers showed a correlation between lesion volume and cognitive performance.

Conclusion: The current findings indicate an increased prevalence of WM hyperintensities in non-carriers compared with carriers of the APOE ε4 allele among patients with AD. This is consistent with a possibly more pronounced contribution of heterogeneous vascular risk factors to WM damage and cognitive impairment in patients with AD without APOE ε4-mediated risk.