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000165248 0247_ $$2doi$$a10.1007/s00401-022-02454-z
000165248 0247_ $$2pmid$$apmid:36066633
000165248 0247_ $$2ISSN$$a0001-6322
000165248 0247_ $$2ISSN$$a1432-0533
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000165248 037__ $$aDZNE-2022-01541
000165248 041__ $$aEnglish
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000165248 1001_ $$0P:(DE-2719)2813349$$aJansen, Iris$$b0$$udzne
000165248 245__ $$aGenome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
000165248 260__ $$aHeidelberg$$bSpringer$$c2022
000165248 3367_ $$2DRIVER$$aarticle
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000165248 520__ $$aAmyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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000165248 650_7 $$2Other$$aAlzheimer’s disease
000165248 650_7 $$2Other$$aAmyloid-beta
000165248 650_7 $$2Other$$aCerebrospinal fluid
000165248 650_7 $$2Other$$aGWAS
000165248 650_7 $$2Other$$aTau
000165248 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000165248 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000165248 650_2 $$2MeSH$$aApolipoproteins E: genetics
000165248 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000165248 650_2 $$2MeSH$$aCell Cycle Proteins
000165248 650_2 $$2MeSH$$aHumans
000165248 650_2 $$2MeSH$$aPeptide Fragments: cerebrospinal fluid
000165248 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000165248 650_2 $$2MeSH$$atau Proteins: genetics
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