Universität zu Köln

Benson, Gloria S., Bauer, Chris, Hausner, Lucrezia, Couturier, Samuel, Lewczuk, Piotr, Peters, Oliver ORCID: 0000-0003-0568-2998, Huell, Michael, Jahn, Holger ORCID: 0000-0003-3607-7651, Jessen, Frank, Pantel, Johannes, Teipel, Stefan J., Wagner, Michael ORCID: 0000-0003-2589-6440, Schuchhardt, Johannes, Wiltfang, Jens, Kornhuber, Johannes and Froelich, Lutz (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. J. Neural Transm., 129 (5-6). S. 477 - 487. WIEN: SPRINGER WIEN. ISSN 1435-1463

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Benson, Gloria S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Hausner, Lucrezia UNSPECIFIED UNSPECIFIED UNSPECIFIED Couturier, Samuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Lewczuk, Piotr UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Oliver UNSPECIFIED orcid.org/0000-0003-0568-2998 UNSPECIFIED Huell, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Jahn, Holger UNSPECIFIED orcid.org/0000-0003-3607-7651 UNSPECIFIED Jessen, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Pantel, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Teipel, Stefan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Michael UNSPECIFIED orcid.org/0000-0003-2589-6440 UNSPECIFIED Schuchhardt, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiltfang, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Kornhuber, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Froelich, Lutz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-694988
DOI:	10.1007/s00702-022-02461-0
Journal or Publication Title:	J. Neural Transm.
Volume:	129
Number:	5-6
Page Range:	S. 477 - 487
Date:	2022
Publisher:	SPRINGER WIEN
Place of Publication:	WIEN
ISSN:	1435-1463
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language APOLIPOPROTEIN-E; DIAGNOSIS; ALLELE; MCI Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69498