Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology modulates cognitive performance

Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean‐Philippe; Henry, Hugues; Gunten, Armin von; Popp, Julius

doi:10.1186/s13195-017-0235-0

Cited by 20 publications

(17 citation statements)

References 68 publications

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“…This threshold optimized the Youden index [30] of the receiver operating characteristic (ROC) curve for the prediction of CDR categories (CDR 0 versus CDR >0) [31]. It was similar to previously reported findings [32].…”

Section: Methodssupporting

confidence: 76%

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

et al. 2017

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BackgroundHyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults.MethodsCross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1–42 peptide chain [Aβ1–42] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status.ResultsThe diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ1–42, tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine, glycine, methionine, SAH, SAM, serine, cysteine, and Hcy and reached a diagnostic accuracy of 87.5%. CSF SAH and 5-MTHF were associated with CSF tau and p-tau181. Plasma one-carbon metabolites were able to diagnose subjects with a positive CSF profile of AD pathology in APOE ε4 carriers.ConclusionsWe observed significant improvements in the prediction of cognitive impairment by adding one-carbon metabolites. This is partially explained by associations with CSF tau and p-tau181, suggesting a role for one-carbon metabolism in the aggregation of tau and neuronal injury. These metabolites may be particularly critical in APOE ε4 carriers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-017-0270-x) contains supplementary material, which is available to authorized users.

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Section: Methodssupporting

confidence: 76%

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

et al. 2017

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“…679 (78%) of the Cardiff sample set were also included in the Oxford sample set. Participants were included in these 'Oxford' and 'Cardiff' sample sets from across three multi-center studies: DESCRIPA [18], EDAR [19], and Pharma-Cog [20], and eight single center studies: Amsterdam [21], Antwerp [22], San Sebastian GAP [23], Gothenburg [24], Barcelona IDIBAPS [25], Lausanne [26], Leuven [27], and Barcelona St Pau [28]. Sample number differences between the 'Oxford' and 'Cardiff' sample sets were necessary due to plasma sample availability.…”

Section: Subjects: Emif-ad Multimodal Biomarker Discovery Study (Emifmentioning

confidence: 99%

Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer’s Disease Multimodal Biomarker Discovery Cohort

Westwood

Baird

Anand

et al. 2020

JAD

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We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E 4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure.

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“…Meanwhile, only a very limited number of studies have examined the relation between neuroticism and in vivo AD biomarkers. One previous study using cerebrospinal fluid (CSF) biomarkers reported no significant association between personality traits including neuroticism and conscientiousness and CSF Aβ 1‐42 and tau levels . Another previous study that measured brain Aβ deposition using PiB‐PET also showed no direct association between neuroticism and global PiB retention .…”

Section: Discussionmentioning

confidence: 95%

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI

Byun

Jung

Sohn

et al. 2020

Psychiatry Clin Neurosci

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Aim It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD‐related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid‐beta (Aβ) burden, AD‐signature regional neurodegeneration, and white matter hyperintensities (WMH) in non‐demented middle‐ and old‐aged adults. Methods A total of 397 non‐demented participants underwent comprehensive clinical and neuropsychological assessments, 11C‐labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five‐Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. Results Neither neuroticism nor conscientiousness was associated with cerebral Aβ deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD‐signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD‐signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aβ deposition or WMH were not. Conclusion The present findings suggest that amyloid‐independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.

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Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology modulates cognitive performance

Cited by 20 publications

References 68 publications

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

Validation of Plasma Proteomic Biomarkers Relating to Brain Amyloid Burden in the EMIF-Alzheimer’s Disease Multimodal Biomarker Discovery Cohort

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI

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