Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network

Benson GS, Bauer C, Hausner L, Couturier S, Lewczuk P, Peters O, Huell M, Jahn H, Jessen F, Pantel J, Teipel SJ, Wagner M, Schuchhardt J, Wiltfang J, Kornhuber J, Froelich L (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Journal of Neural Transmission Springer Nature

DOI: 10.1007/s00702-022-02461-0

Abstract

ApoE4, the strongest genetic risk factor for Alzheimer's disease (AD), has been shown to be associated with both beta-amyloid (A beta) and tau pathology, with the strongest evidence for effects on A beta, while the association between ApoE4 and tau pathology remains inconsistent. This study aimed to investigate the associations between ApoE4 with CSF A beta 42, total tau (t-tau), phospho-tau181 (p-tau), and with the progression of decline in a large cohort of MCI subjects, both progressors to AD and other dementias, as well as non-progressors. We analyzed associations of CSF A beta 42, p-tau and t-tau with ApoE4 allele frequency cross-sectionally and longitudinally over 3 years of follow-up in 195 individuals with a diagnosis of MCI-stable, MCI-AD converters and MCI progressing to other dementias from the German Dementia Competence Network. In the total sample, ApoE4 carriers had lower concentrations of CSF A beta 42, and increased concentrations of t-tau and p-tau compared to non-carriers in a gene dose-dependent manner. Comparisons of these associations stratified by MCI-progression groups showed a significant influence of ApoE4 carriership and diagnostic group on all CSF biomarker levels. The effect of ApoE4 was present in MCI-stable individuals but not in the other groups, with ApoE4 + carriers having decreased CSF A beta 42 levels, and increased concentration of t-tau and p-tau. Longitudinally, individuals with abnormal t-tau and A beta 42 had a more rapid progression of cognitive and clinical decline, independently of ApoE4 genotype. Overall, our results contribute to an emerging framework in which ApoE4 involves mechanisms associated with both CSF amyloid-beta burden and tau aggregation at specific time points in AD pathogenesis.

Authors with CRIS profile

Piotr Lewczuk Medizinische Fakultät Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) MicroDiscovery GmbH DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universität zu Köln DE Germany (DE) Goethe-Universität Frankfurt am Main DE Germany (DE) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE)

How to cite

APA:

Benson, G.S., Bauer, C., Hausner, L., Couturier, S., Lewczuk, P., Peters, O.,... Froelich, L. (2022). Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network. Journal of Neural Transmission. https://doi.org/10.1007/s00702-022-02461-0

MLA:

Benson, Gloria S., et al. "Don't forget about tau: the effects of ApoE4 genotype on Alzheimer's disease cerebrospinal fluid biomarkers in subjects with mild cognitive impairment-data from the Dementia Competence Network." Journal of Neural Transmission (2022).

BibTeX: Download