Dataset Information

The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer's Disease: Exploring Interactions With Sex.

ABSTRACT:

Background

Sex-related difference in Alzheimer's disease (AD) has been proposed, and apolipoprotein E (ApoE) isoforms have been suggested to be involved in the pathogenesis of AD.

Objective

We aimed to explore whether cerebrospinal fluid (CSF) ApoE is associated with AD biomarkers and whether the associations are different (between sexes).

Methods

Data of 309 participants [92 with normal cognition, 148 with mild cognitive impairment (MCI), and 69 with AD dementia] from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were cross-sectionally evaluated with the multiple linear regression model and longitudinally with the multivariate linear mixed-effects model for the associations of CSF ApoE with AD biomarkers. Sex-ApoE interaction was used to estimate whether sex moderates the associations of CSF ApoE and AD biomarkers.

Results

Significant interactions between CSF ApoE and sex on AD biomarkers were observed [amyloid-β (Aβ): p = 0.0169 and phosphorylated-tau (p-tau): p = 0.0453]. In women, baseline CSF ApoE levels were significantly associated with baseline Aβ (p = 0.0135) and total-tau (t-tau) (p < 0.0001) as well as longitudinal changes of the biomarkers (Aβ: p = 0.0104; t-tau: p = 0.0110). In men, baseline CSF ApoE levels were only correlated with baseline p-tau (p < 0.0001) and t-tau (p < 0.0001) and did not aggravate AD biomarkers longitudinally.

Conclusion

The associations between CSF ApoE and AD biomarkers were sex-specific. Elevated CSF ApoE was associated with longitudinal changes of AD biomarkers in women, which indicates that CSF ApoE might be involved in the pathogenesis of AD pathology in a sex-specific way.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7968417 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer's Disease: Exploring Interactions With Sex.

Liu Ying Y Song Jing-Hui JH Xu Wei W Hou Xiao-He XH Li Jie-Qiong JQ Yu Jin-Tai JT Tan Lan L Chi Song S

Frontiers in neuroscience 20210303

<h4>Background</h4>Sex-related difference in Alzheimer's disease (AD) has been proposed, and apolipoprotein E (ApoE) isoforms have been suggested to be involved in the pathogenesis of AD.<h4>Objective</h4>We aimed to explore whether cerebrospinal fluid (CSF) ApoE is associated with AD biomarkers and whether the associations are different (between sexes).<h4>Methods</h4>Data of 309 participants [92 with normal cognition, 148 with mild cognitive impairment (MCI), and 69 with AD dementia] from the ...[more]

PMID: 33746700

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Project description:Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

Dataset Information

The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer's Disease: Exploring Interactions With Sex.

Background

Objective

Methods

Results

Conclusion

Publications

The Associations of Cerebrospinal Fluid ApoE and Biomarkers of Alzheimer's Disease: Exploring Interactions With Sex.

Similar Datasets

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