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, Gloria S.; Bauer, Chris; Hausner, Lucrezia; Couturier, Samuel; Lewczuk, Piotr; Peters, Oliver; Huell, Michael; Jahn, Holger; Jessen, Frank; Pantel, Johannes; Teipel, Stefan J.; Wagner, Michael; Schuchhardt, Johannes; Wiltfang, Jens; Kornhuber, Johannes und 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. In: Journal of Neural Transmission, Bd. 129, Nr. 5-6: S. 477-486

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0300-9564
• Sprache: Englisch