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- Titel:
Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- Dokumenttyp:
- Article; Journal Article; Meta-Analysis
- Autor(en):
- Abstract:
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
- Zeitschriftentitel:
- Acta Neuropathol (Berl)
- Jahr:
- 2022
- Band / Volume:
- 144
- Heft / Issue:
- 5
- Seitenangaben Beitrag:
- 821-842
- Volltext / DOI:
- doi:10.1007/s00401-022-02454-z
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/36066633
- Print-ISSN:
- 0001-6322
- TUM Einrichtung:
- 1310; 1367; 55; Klinik und Poliklinik für Psychiatrie und Psychotherapie
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