Relations between personality changes and cerebrospinal fluid biomarkers of Alzheimer's disease pathology

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

doi:10.1016/j.jpsychires.2016.12.024

Cited by 28 publications

(20 citation statements)

References 54 publications

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“…For example, MCI patients have higher neuroticism and lower conscientiousness than CN individuals, which is consistent with the present findings (Table ). In addition, changes in personality traits, particularly increased neuroticism and decreased conscientiousness compared to retrospectively assessed personality, were associated with lower CSF Aβ42 concentrations . However, given that associations of personality traits, including neuroticism and conscientiousness, with AD‐CT were significant even after controlling the effect of clinical diagnosis (CN vs MCI), our finding supports more of the hypothesis that a certain type of personality trait might be a risk factor of developing AD, rather than an outcome of reverse causality.…”

Section: Discussionsupporting

confidence: 55%

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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Section: Discussionsupporting

confidence: 55%

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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“…Participants with AD were recruited among patients with cognitive impairment attending the Memory Clinics of the Department of Psychiatry and the Department of Clinical Neurosciences at Lausanne University Hospital for the diagnosis of their complaints [21]. Control subjects were recruited by announcements and word of mouth.…”

Section: Methodsmentioning

confidence: 99%

Systemic and central nervous system metabolic alterations in Alzheimer’s disease

et al. 2019

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BackgroundMetabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer’s disease (AD) on both the systemic and central nervous system level. To study the extent and significance of these alterations in AD, quantitative metabolomics was applied to plasma and cerebrospinal fluid (CSF) from clinically well-characterized AD patients and cognitively healthy control subjects. The observed metabolic alterations were associated with core pathological processes of AD to investigate their relation with amyloid pathology and tau-related neurodegeneration.MethodsIn a case-control study of clinical and biomarker-confirmed AD patients (n = 40) and cognitively healthy controls without cerebral AD pathology (n = 34) with paired plasma and CSF samples, we performed metabolic profiling, i.e., untargeted metabolomics and targeted quantification. Targeted quantification focused on identified deregulated pathways highlighted in the untargeted assay, i.e. the TCA cycle, and its anaplerotic pathways, as well as the neuroactive tryptophan and kynurenine pathway.ResultsConcentrations of several TCA cycle and beta-oxidation intermediates were higher in plasma of AD patients, whilst amino acid concentrations were significantly lower. Similar alterations in these energy metabolism intermediates were observed in CSF, together with higher concentrations of creatinine, which were strongly correlated with blood-brain barrier permeability. Alterations of several amino acids were associated with CSF Amyloidβ1–42. The tryptophan catabolites, kynurenic acid and quinolinic acid, showed significantly higher concentrations in CSF of AD patients, which, together with other tryptophan pathway intermediates, were correlated with either CSF Amyloidβ1–42, or tau and phosphorylated Tau-181.ConclusionsThis study revealed AD-associated systemic dysregulation of nutrient sensing and oxidation and CNS-specific alterations in the neuroactive tryptophan pathway and (phospho)creatine degradation. The specific association of amino acids and tryptophan catabolites with AD CSF biomarkers suggests a close relationship with core AD pathology.Our findings warrant validation in independent, larger cohort studies as well as further investigation of factors such as gender and APOE genotype, as well as of other groups, such as preclinical AD, to identify metabolic alterations as potential intervention targets.

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“…A pathological AD CSF biomarker profile was defined as CSF P-tau181/Aβ 1–42 ratio > 0.0779 (i.e., “high” ratio for positive CSF profile of AD pathology), based on clinical study site data [ 39 ] and in line with previous work (i.e., 0.08) [ 40 ]. The cutoff optimized the Youden index [ 41 ] of the ROC curve for the prediction of CDR categories (CDR = 0 versus CDR > 0) as previously reported [ 27 ], where the cutoff for CSF P-tau181/Aβ 1–42 ratio was further confirmed to be a highly significant predictor of cognitive decline.…”

Section: Methodsmentioning

confidence: 99%

Alzheimer disease pathology and the cerebrospinal fluid proteome

Dayon

Galindo

Wojcik³

et al. 2018

Alz Res Therapy

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BackgroundAltered proteome profiles have been reported in both postmortem brain tissues and body fluids of subjects with Alzheimer disease (AD), but their broad relationships with AD pathology, amyloid pathology, and tau-related neurodegeneration have not yet been fully explored. Using a robust automated MS-based proteomic biomarker discovery workflow, we measured cerebrospinal fluid (CSF) proteomes to explore their association with well-established markers of core AD pathology.MethodsCross-sectional analysis was performed on CSF collected from 120 older community-dwelling adults with normal (n = 48) or impaired cognition (n = 72). LC-MS quantified hundreds of proteins in the CSF. CSF concentrations of β-amyloid 1–42 (Aβ1–42), tau, and tau phosphorylated at threonine 181 (P-tau181) were determined with immunoassays. First, we explored proteins relevant to biomarker-defined AD. Then, correlation analysis of CSF proteins with CSF markers of amyloid pathology, neuronal injury, and tau hyperphosphorylation (i.e., Aβ1–42, tau, P-tau181) was performed using Pearson’s correlation coefficient and Bonferroni correction for multiple comparisons.ResultsWe quantified 790 proteins in CSF samples with MS. Four CSF proteins showed an association with CSF Aβ1–42 levels (p value ≤ 0.05 with correlation coefficient (R) ≥ 0.38). We identified 50 additional CSF proteins associated with CSF tau and 46 proteins associated with CSF P-tau181 (p value ≤ 0.05 with R ≥ 0.37). The majority of those proteins that showed such associations were brain-enriched proteins. Gene Ontology annotation revealed an enrichment for synaptic proteins and proteins originating from reelin-producing cells and the myelin sheath.ConclusionsWe used an MS-based proteomic workflow to profile the CSF proteome in relation to cerebral AD pathology. We report strong evidence of previously reported CSF proteins and several novel CSF proteins specifically associated with amyloid pathology or neuronal injury and tau hyperphosphorylation.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0397-4) contains supplementary material, which is available to authorized users.

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Relations between personality changes and cerebrospinal fluid biomarkers of Alzheimer's disease pathology

Cited by 28 publications

References 54 publications

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

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

Systemic and central nervous system metabolic alterations in Alzheimer’s disease

Alzheimer disease pathology and the cerebrospinal fluid proteome

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