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- Title
Apolipoprotein E Genotype and the Diagnostic Accuracy of Cerebrospinal Fluid Biomarkers for Alzheimer Disease.
- Authors
Lautner, Ronald; Palmqvist, Sebastian; Mattsson, Niklas; Andreasson, Ulf; Wallin, Anders; Pálsson, Erik; Jakobsson, Joel; Herukka, Sanna-Kaisa; Owenius, Rikard; Olsson, Bob; Hampel, Harald; Rujescu, Dan; Ewers, Michael; Landén, Mikael; Minthon, Lennart; Blennow, Kaj; Zetterberg, Henrik; Hansson, Oskar
- Abstract
IMPORTANCE Several studies suggest that the apolipoprotein E (APOE) E4 allele modulates jamapsychiatry.com cerebrospinal fluid (CSF) levels of ß-amyloid 42 (Aß42). Whether this effect is secondary to the association of the APOE E4 allele with cortical Aß deposition or whether APOE E4 directly influences CSF levels of Aß42 independently of Aß pathology remains unknown. OBJECTIVE To evaluate whether the APOE genotype affects the diagnostic accuracy of CSF biomarkers for Alzheimer disease (AD), in particular Aß42 levels, and whether the association of APOE E4 with CSF biomarkers depends on cortical Aß status. DESIGN, SETTING, AND PARTICIPANTS We collected data from 4 different centers in Sweden, Finland, and Germany. Cohort A consisted of 1345 individuals aged 23 to 99 years with baseline CSF samples, including 309 with AD, 287 with prodromal AD, 399 with stable mild cognitive impairment, 99 with dementias other than AD, and 251 controls. Cohort B included 105 nondemented younger individuals (aged 20-34 years) with CSF samples available. Cohort C included 118 patients aged 60 to 80 years with mild cognitive symptoms who underwent flutemetamol F18 ([18F]flumetamol) positron emission tomography amyloid imaging and CSF tap. EXPOSURES Standard care. MAIN OUTCOMES AND MEASURES Cerebrospinal fluid levels of Aß42 and total and phosphorylated tau in relation to the APOE E2/E3/E4 polymorphism in different diagnostic groups and in cases with or without cortical uptake of [18F]flutemetamol. RESULTS The CSF levels of Aß42 but not total and phosphorylated tau were lower in APOE E4 carriers compared with noncarriers irrespective of diagnostic group (cohort A). Despite this, CSF levels of Aß42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P < .001 to P = .006). Multiple binary logistic regression revealed that CSF levels of Aß42 and APOE E4 genotype were independent predictors of AD diagnosis. In cohort B, APOE E4 carrier status did not influence CSF levels of Aß42. Moreover, when stratifying for cortical uptake of ['8F]flutemetamol in cohort C, APOE E4 genotype did not influence CSF levels of Aß42. This result was replicated in a cohort with individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) using carbon 11-labeled Pittsburgh Compound B scanning. CONCLUSIONS AND RELEVANCE Cerebrospinal fluid levels of Aß42 are strongly associated with the diagnosis of AD and cortical Aß accumulation independent of APOE genotype. The clinical cutoff for CSF levels of Aß42 should be the same for all APOE genotypes.
- Subjects
ALZHEIMER'S disease; APOLIPOPROTEIN E; CEREBROSPINAL fluid; BIOMARKERS; POSITRON emission tomography
- Publication
JAMA Psychiatry, 2014, Vol 71, Issue 10, p1183
- ISSN
2168-622X
- Publication type
Article
- DOI
10.1001/jamapsychiatry.2014.1060