Dataset Information

ABCA7 genotype altered A? levels in cerebrospinal fluid in Alzheimer's disease without dementia.

ABSTRACT: Background:ATP-binding cassette transporter A7 (ABCA7) rs3764650 has been identified to be a susceptibility locus for Alzheimer's disease (AD), but its role in cerebrospinal fluid (CSF) proteins was still unclear. Methods:The associations of rs3764650 with CSF A?1-42, t-tau and p-tau were analyzed in non-dementia AD, including preclinical and prodromal AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Results:Finally, GG + GT genotypes significantly decreased CSF A?1-42 level, but did not alter CSF t-tau and p-tau levels in non-dementia AD at baseline, which was further confirmed in longitudinal studies. Conclusions:Our findings supported that ABCA7 modified AD risk by altering A? deposition rather than tau pathology.

SUBMITTER: Ma FC

PROVIDER: S-EPMC6281527 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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ABCA7 genotype altered Aβ levels in cerebrospinal fluid in Alzheimer's disease without dementia.

Ma Fang-Chen FC Zong Yu Y Wang Hui-Fu HF Li Jie-Qiong JQ Cao Xi-Peng XP Tan Lan L

Annals of translational medicine 20181101 22

<h4>Background</h4>ATP-binding cassette transporter A7 (ABCA7) rs3764650 has been identified to be a susceptibility locus for Alzheimer's disease (AD), but its role in cerebrospinal fluid (CSF) proteins was still unclear.<h4>Methods</h4>The associations of rs3764650 with CSF Aβ<sub>1-42</sub>, t-tau and p-tau were analyzed in non-dementia AD, including preclinical and prodromal AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.<h4>Results</h4>Finally, GG + GT genotypes signif ...[more]

PMID: 30596067

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Project description:BackgroundAlthough saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are important structural components of neuronal membranes and precursors of signaling molecules, knowledge of their metabolism in Alzheimer's disease (AD) is limited. Based on recent discovery that lipids in cerebrospinal fluid (CSF) are distributed in both brain-derived nanoparticles (NP) and supernatant fluid (SF), we hypothesized that fatty acid (FA) abundance and distribution into these compartments is altered in early AD pathology.Methodology and findingsWe assayed the FA composition and abundance in CSF fractions from cognitively healthy (CH), mild cognitive impairment (MCI), and AD study participants using gas chromatography-mass spectrometry. In the SF fraction, concentration of docosahexaenoic acid [DHA, (C22:6n-3)] was less in AD compared with CH, while alpha linolenic acid [α-LNA, (C18:3n-3)] was lower in MCI compared with CH. In the NP fraction, levels of SAFAs (C15:0, C16:0) and a MUFA (C15:1) differentiated CH from MCI, while two MUFAs (C15:1, C19:1) and four PUFAs (C20:2n-6, C20:3n-3, C22:4n-6, C22:5n-3) were higher in AD compared with CH. Levels of even-chain free SAFA and total free FA levels were higher in AD, levels of odd-chain free SAFAs, MUFAs, n-3 PUFAs, and total PUFA, were lower in AD compared with CH. Free n-6 PUFA levels were similar in all three groups.Conclusions and significanceFA metabolism is compartmentalized differently in NP versus SF fractions of CSF, and altered FA levels reflect the importance of abnormal metabolism and oxidative pathways in AD. Depleted DHA in CSF fractions in AD is consistent with the importance of n-3 PUFAs in cognitive function, and suggests that disturbed PUFA metabolism contributes to AD pathology. This study of FA levels in CSF fractions from different cognitive stages shows potential AD biomarkers, and provides further insight into cell membrane dysfunctions, including mechanisms leading to amyloid production.

Dataset Information

ABCA7 genotype altered A? levels in cerebrospinal fluid in Alzheimer's disease without dementia.

Publications

ABCA7 genotype altered Aβ levels in cerebrospinal fluid in Alzheimer's disease without dementia.

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