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Kühn, A.L.* ; Frenzel, S.* ; Teumer, A.* ; Wittfeld, K.* ; Garvert, L.* ; Weihs, A.* ; Homuth, G.* ; Prokisch, H. ; Bülow, R.* ; Nauck, M.* ; Völker, U.* ; Völzke, H.* ; Grabe, H.J.* ; Van der Auwera, S.*

TREML2 gene expression and its missense variant rs3747742 associate with white matter hyperintensity volume and Alzheimer's disease-related brain atrophy in the general population.

Int. J. Mol. Sci. 23:13764 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Although the common pathology of Alzheimer's disease (AD) and white matter hyperintensities (WMH) is disputed, the gene TREML2 has been implicated in both conditions: its whole-blood gene expression was associated with WMH volume and its missense variant rs3747742 with AD risk. We re-examined those associations within one comprehensive dataset of the general population, additionally searched for cross-relations and illuminated the role of the apolipoprotein E (APOE) ε4 status in the associations. For our linear regression and linear mixed effect models, we used 1949 participants from the Study of Health in Pomerania (Germany). AD was assessed using a continuous pre-symptomatic MRI-based score evaluating a participant's AD-related brain atrophy. In our study, increased whole-blood TREML2 gene expression was significantly associated with reduced WMH volume but not with the AD score. Conversely, rs3747742-C was significantly associated with a reduced AD score but not with WMH volume. The APOE status did not influence the associations. In sum, TREML2 robustly associated with WMH volume and AD-related brain atrophy on different molecular levels. Our results thus underpin TREML2's role in neurodegeneration, might point to its involvement in AD and WMH via different biological mechanisms, and highlight TREML2 as a worthwhile target for disentangling the two pathologies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alzheimer’s Disease ; Treml2 ; Apolipoprotein E ; Brain Atrophy ; Gene Expression ; General Population ; Immune System ; Neurodegeneration ; Rs3747742 ; White Matter Hyperintensity
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 23, Heft: 22, Seiten: , Artikelnummer: 13764 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
Fresenius Medical Care North America
nterSystems GmbH
German Federal State of Mecklenburg-Western Pomerania