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3.
Postgrad Med ; 131(7): 501-508, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483196

RESUMO

Objectives: Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) is a longitudinal ongoing study initiated in 2018 that takes place in the Cognitive Disorders Clinic of Aiginition Hospital of the National and Kapodistrian University of Athens. Its aim is to address several research questions concerning the preclinical and prodromal stage of Alzheimer's disease and explore potential markers for early detection, prediction, and primary prevention of dementia. Methods: We here present the design and the preliminary baseline characteristics of ALBION. The sample of our study consists of people aged over 50 who are concerned about their memory but are cognitively normal (CN) or have mild cognitive deficits. Each participant undergoes an extensive assessment including several demographic, medical, social, environmental, clinical, nutritional, neuropsychological determinants and lifestyle activities. Furthermore, we are collecting data from portable devices, neuroimaging techniques and biological samples (blood, stools, CSF). All participants are assessed annually for a period of 10 years. Results: In total, 47 participants have completed the initial evaluation up to date and are divided in two groups, CN individuals (N = 26) and MCI patients (N = 21), based on their cognitive status. The participants are, on average, 64 years old, 46.3% of the sample is male with an average of 12.73 years of education. MCI patients report more comorbidities and have a lower score in the MMSE test. Regarding APOE status, 2 participants are ε4 homozygotes and 10 ε4 heterozygotes. CSF analyses (Aß42, Τ-tau, P-tau) revealed no differences between the two groups. Conclusion: The ALBION study offers an opportunity to explore preclinical dementia and identify new and tailored markers, particularly relating to lifestyle. Further investigation of these populations may provide a wider profile of the changes taking place in the preclinical phase of dementia, leading to potentially effective therapeutic and preventive strategies.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/metabolismo , Prevenção Primária , Sintomas Prodrômicos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Diagnóstico Precoce , Eletroencefalografia , Feminino , Neuroimagem Funcional , Grécia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Dados Preliminares , Proteínas tau/líquido cefalorraquidiano
4.
Clin Biochem ; 72: 15-23, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31194969

RESUMO

During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection. Meanwhile harmonized staging systems emerged in order to increase inter rater reproducibility. Therefore, a refined definition of Alzheimer's disease was recommended., a clearer picture of the neuropathological lesions diversity emerged secondarily to the systematic assessment of concomitant pathology highlighting finally a low rate of pure AD pathology. This brings new challenges to laboratory medicine in the field of cerebrospinal fluid (CSF) markers of Alzheimer's disease: how to further validate total Tau, phospho-TAU, Aß40 and Aß42 and new marker level cut-offs while autopsy rates are declining?


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/normas , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/química , Encéfalo/patologia , Progressão da Doença , Humanos , Fosforilação , Proteínas tau/química , Proteínas tau/normas
5.
Braz J Psychiatry ; 41(6): 479-484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31166546

RESUMO

OBJECTIVE: The relationship between biomarkers of amyloid-beta aggregation (Aß1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses. METHODS: We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer's disease (AD), and 26 with other dementias (OD). RESULTS: MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aß1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aß1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001). CONCLUSION: CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Análise de Variância , Biomarcadores/líquido cefalorraquidiano , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Valores de Referência , Estatísticas não Paramétricas
6.
BMC Neurol ; 19(1): 113, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164098

RESUMO

BACKGROUND AND AIM: Toxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid ß 1-42 (Aß1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD. METHODS: Twenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aß1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated. RESULTS: CSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aß1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aß1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins. CONCLUSION: CSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aß1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , alfa-Sinucleína/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia
7.
J Neurol ; 266(9): 2304-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31179518

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly used to diagnose Alzheimer's disease (AD). However, important methodological and technical remain regarding measurement variability between kit providers and users. We compared the Lumipulse fully automated assays with the manual INNOTEST assays (both from Fujirebio Europe NV, Gent, Belgium) on a clinically representative sample of patients and controls. METHODS: CSF samples of 156 patients were used to quantify Amyloïd Aß1-42 peptide (Aß1-42) and Total-Tau (T-Tau) protein by chemiluminescent enzyme-immunoassay (Lumipulse). Patients were divided into several subgroups: Alzheimer (AD = 44), mild-cognitive impairment (MCI = 23), other dementias (OD = 36), non-dementing neurological conditions (ND = 11), and controls (CTRL = 42). Clinical cut-offs were determined by comparing AD and CTRL with ROC curves for the two markers and their related ratio (T-Tau/Aß1-42). Subgroups of 58 (for phosphorylated-Tau) and 115 samples (for Aß1-42 and T-Tau) were used to evaluate the concordance of this analyzer with the INNOTEST assays. RESULTS: Lumipulse and INNOTEST assays showed good concordance for all markers, but systematic bias was observed justifying the need to redefine new clinical cut-offs. To discriminate AD from CTRL subjects, T-Tau/Aß1-42 ratio was the best biomarker, with a cut-off value of 1.12 (sensitivity 81.8% and specificity 92.9%). Similar clinical performances were observed for the Lumipulse and Innotests assays on the subsample of 115 subjects. CONCLUSIONS: Our results demonstrate that the Lumipulse Aß1-42 and T-Tau assays show good analytical and clinical performances in the context of patient evaluation referred to a memory clinic. Automated analyzers should be preferred for the measurement of CSF AD biomarkers to reduce inter- and intra-laboratory variability.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Técnicas Imunoenzimáticas/métodos , Medições Luminescentes/métodos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/análise , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Técnicas Imunoenzimáticas/normas , Medições Luminescentes/normas , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Proteínas tau/análise
8.
Acta Neurol Scand ; 140(2): 147-156, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31070772

RESUMO

BACKGROUND: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. AIMS: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders. METHODS: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. RESULTS: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P = 0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P = 0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P < 0.001). CONCLUSION: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies.


Assuntos
Proteínas de Neurofilamentos/líquido cefalorraquidiano , Transtornos Parkinsonianos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/mortalidade , Transtornos Parkinsonianos/patologia
9.
Clin Chim Acta ; 495: 451-456, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31051163

RESUMO

CONTEXT: Cerebrospinal fluid (CSF) biomarkers are valuable tools for the diagnosis of neurological diseases. We aimed to investigate within a retrospective multicentric study the final diagnosis associated with very high CSF Tau levels and to identify patterns of biomarkers that would differentiate them in clinical practice, to help clinical biologists into physicians' counseling. PATIENTS AND METHODS: Within the national multicentric network ePLM, we included 1743 patients from January 1, 2008, to December 31, 2013, with CSF biomarkers assayed by the same Innotest assays (protein Tau, phospho-Tau [pTau], and Aß 1-42). We identified 205 patients with protein Tau concentration higher than 1200 pg/mL and final diagnosis. RESULTS: Among those patients, 105 (51.2%) were suffering from Alzheimer's disease, 37 (18%) from sporadic Creuztfeldt-Jakob disease, and 63 (30.7%) from other neurological diseases including paraneoplastic/ central nervous system tumor, frontotemporal dementia, other diagnoses, amyloid angiopathy, Lewy body dementia, and infections of the central nervous system. Phospho-Tau, Aß1-42 and Aß1-42/pTau values differed significantly between the three groups of patients (p < .001). An Aß1-42/pTau ratio between 4.7 and 9.7 was suggestive of other neurological diseases (threshold in AD: 8.3). CSF 14-3-3 was useful to discriminate Alzheimer's disease from Creuztfeldt-Jakob disease in case of Aß1-42 concentrations <550 pg/mL or pTau>60 pg/mL. CONCLUSION: This work emphasizes the interest of a well-thought-out interpretation of CSF biomarkers in neurological diseases, particularly in the case of high Tau protein concentrations in the CSF.


Assuntos
Laboratórios , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/líquido cefalorraquidiano , Adulto Jovem , Proteínas tau/metabolismo
10.
Neurobiol Aging ; 79: 131-141, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31055223

RESUMO

Amyloid ß (Aß) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aß and tau for cognitive impairment in early AD was examined with cross-sectional analysis, measured by cerebrospinal fluid biomarkers (Aß1-42, total tau [t-tau], and phosphorylated tau [p-tau181P]), and on cognitive performance by the repeatable battery for assessment of neuropsychological status (RBANS). Participants (n = 246) included cognitively normal (Aß-), mild cognitively impaired (Aß-), preclinical AD (Aß+), and prodromal AD (Aß+). Overall, cognitive scores (RBANS total scale score) had a moderate negative correlation to t-tau (n = 246; r = -0.434; p < 0.001) and p-tau181P (r = -0.389; p < 0.001). When classified by Aß status, this correlation to t-tau was applicable only in Aß+ participants (n = 139; r = -0.451, p < 0.001) but not Aß- participants (n = 107; r = 0.137, p = 0.16), with identical findings for p-tau. Both tau (p < 0.0001) and interaction of Aß1-42 with tau (p = 0.006) affected RBANS, but not Aß1-42 alone. Cognitive/memory performance correlated well with cerebrospinal fluid tau levels across early stages of AD, although the correlation is Aß dependent.


Assuntos
Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cognição , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
11.
Neurology ; 92(23): e2699-e2705, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31068481

RESUMO

OBJECTIVE: To identify potential predictors for outcome in individuals with mild cognitive impairment (MCI) who have reverted to normal cognition (NC). METHODS: We selected individuals with MCI, who reverted at follow-up to NC, with follow-up after reversion from Alzheimer's Disease Neuroimaging Initiative. Common clinical markers, Alzheimer disease (AD) biomarkers, and neurodegeneration imaging markers were used to compare MCI reverters based on subsequent clinical outcome (i.e., subsequent decline or stable reversion). For independent comparison, findings of the clinical Amsterdam Dementia Cohort are presented. RESULTS: Seventy-seven (10%) out of 757 individuals with MCI reverted to NC and 61 of these individuals had follow-up data available. After 3.2 ± 2.2 years, 16 (24%) progressed to MCI, and 3 (5%) to dementia. Those who declined were older and had a higher amyloid PET burden and higher CSF tau levels. CONCLUSION: In MCI reverters, abnormal biomarkers for AD pathology are associated with subsequent decline. AD biomarkers may aid in the prognosis of reverting MCI.


Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Demência/epidemiologia , Placa Amiloide/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Compostos de Anilina , Biomarcadores , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/epidemiologia , Progressão da Doença , Etilenoglicóis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons , Prognóstico , Recidiva , Remissão Espontânea , Medição de Risco , Tiazóis , Proteínas tau/líquido cefalorraquidiano
12.
Neurology ; 92(23): e2717-e2726, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31068482

RESUMO

OBJECTIVE: To identify CSF biomarkers that are related to decreased white matter (WM) integrity and poor cognitive performance in former professional athletes with a history of multiple concussions. METHODS: Concentrations of phosphorylated tau181, total tau (t-tau), and ß-amyloid in the CSF were measured in 3 groups: 22 former professional athletes with multiple concussions (mean ± SD age 55.9 ± 12.2 years), 5 healthy controls (age 57.4 ± 5.2 years), and 12 participants (age 60.0 ± 6.6 years) diagnosed with Alzheimer disease (AD). All participants in the former athletes group underwent diffusion tensor imaging to determine WM tract integrity and completed neuropsychological testing. We divided the former athletes group into those with normal (<300 pg/mL) and high (>300 pg/mL) CSF t-tau. RESULTS: CSF t-tau in the former athletes group was significantly higher than in the healthy control group (349.3 ± 182.6 vs 188.8 ± 39.9 pg/mL, p = 0.003) and significantly lower than in the patients with AD (349.3 ± 182.6 vs 857.0 ± 449.3 pg/mL, p = 0.007). Fractional anisotropy values across all the tracts were significantly lower in the high CSF t-tau group compared to the normal CSF t-tau group (p = 0.036). Participants in the high CSF t-tau group scored significantly lower on the Trail Making Test (TMT) Part B compared to the normal CSF t-tau group (t scores 45.6 ± 18.8 vs 62.3 ± 10.1, p = 0.017). CONCLUSION: Our findings indicate that former athletes with multiple concussions are at increased risk of elevated levels of CSF t-tau and that high CSF t-tau is associated with reduced WM integrity and worse scores on the TMT Part B.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Atletas , Concussão Encefálica/líquido cefalorraquidiano , Cognição , Fragmentos de Peptídeos/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/psicologia , Estudos de Casos e Controles , Encefalopatia Traumática Crônica , Imagem de Tensor de Difusão , Futebol Americano/lesões , Hóquei/lesões , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esqui/lesões , Teste de Sequência Alfanumérica
13.
Acta Neurol Scand ; 140(3): 177-183, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31087810

RESUMO

BACKGROUND: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. AIMS: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. METHODS: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. RESULTS: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1) years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. CONCLUSION: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations.


Assuntos
Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/patologia
14.
Nutrients ; 11(5)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126170

RESUMO

As malnutrition is common in patients with Alzheimer's disease (AD), we evaluated nutritional status and body composition of patients with AD, mild cognitive impairment (MCI) and controls, and studied associations of AD biomarkers and cognitive performance with nutritional status and body composition. We included 552 participants, of which 198 patients had AD, 135 patients had MCI and 219 controls. We assessed nutritional status (mini nutritional assessment (MNA)) and body composition (body mass index (BMI), fat-free mass (FFM) and waist circumference). Linear regression analyses (adjusted for age, gender and education where appropriate) were applied to test associations of AD biomarkers and cognitive performance on five domains with nutritional parameters (dependent). Patients with MCI and AD had a lower BMI and MNA score than controls. Worse performance in all cognitive domains was associated with lower MNA score, but not with body composition. AD biomarkers were associated with MNA score, BMI and waist circumference, and associations with MNA score remained after adjustment for cognitive performance. Both AD biomarkers and cognitive performance were associated with nutritional status, associations with AD biomarkers remained after adjustment for cognition. Our data suggest that malnutrition is not only related to impaired cognition but also to AD pathology.


Assuntos
Doença de Alzheimer/psicologia , Composição Corporal , Cognição , Disfunção Cognitiva/psicologia , Desnutrição/fisiopatologia , Estado Nutricional , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína E4/genética , Biomarcadores/líquido cefalorraquidiano , Índice de Massa Corporal , Estudos de Casos e Controles , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Estudos Prospectivos , Fatores de Risco , Circunferência da Cintura , Proteínas tau/líquido cefalorraquidiano
15.
Clin Biochem ; 72: 30-38, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31129184

RESUMO

BACKGROUND: Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials. METHODS: Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts. RESULTS: Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80-1300 pg/mL; 8-120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays. CONCLUSIONS: Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice.


Assuntos
Imunoensaio/métodos , Proteínas tau/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/química , Humanos , Limite de Detecção , Fosforilação , Reprodutibilidade dos Testes , Proteínas tau/química
16.
Eur J Clin Microbiol Infect Dis ; 38(8): 1443-1447, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093802

RESUMO

Biomarkers classically studied in Alzheimer's disease have been analyzed in numerous central nervous system infections in adults, but there are scarce data on these biomarkers in children. Enteroviruses appear to be the most common cause of aseptic meningitis throughout the world. The aim of the study was to investigate neuroinflammatory properties of non-polio enteroviruses by measuring CSF concentrations of biomarkers that are involved in neuropathological pathways of neurodegenerative disorders. We measured Aß42, t-tau, and S100B concentrations in 42 children with enteroviral meningitis (EM) compared to control group without central nervous system infection. We found enteroviral meningitis (EM) to reduce CSF concentration of Aß42 (median, 1051.1 pg/mL; interquartile range (IQR), 737.6-1559.5 vs. median, 459.4 pg/mL; IQR, 312.0-662.0, p < 0.001). In contrast, CSF concentrations of t-tau and S100B were not affected by EM. There was a correlation between total neutrophil count in CSF and Aß42 (R = - 0.59, p < 0.001). Absolute number of mononuclear cells in the CSF correlated with CSF t-tau (R = 0.41, p < 0.05). Both correlations remained significant after adjustment for age, blood leukocytes, serum CRP, CSF leukocytes, and CSF protein concentration.


Assuntos
Peptídeos beta-Amiloides/líquido cefalorraquidiano , Infecções por Enterovirus/líquido cefalorraquidiano , Meningite Viral/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Adolescente , Biomarcadores/líquido cefalorraquidiano , Criança , Pré-Escolar , Enterovirus , Feminino , Hospitalização , Humanos , Masculino , Polônia , Subunidade beta da Proteína Ligante de Cálcio S100/líquido cefalorraquidiano , Centros de Atenção Terciária , Proteínas tau/líquido cefalorraquidiano
17.
Neurobiol Aging ; 79: 101-109, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31029938

RESUMO

Apolipoprotein E (APOE) ε4 genotype is associated with increased cerebral amyloid beta (Aß) deposition in nondemented elderly and suggested to influence ApoE as well as ApoJ (clusterin [Clu]) and ApoA1 expression. We aimed to assess whether APOE affects early Alzheimer's disease pathophysiology via these apolipoproteins. Cerebrospinal fluid (CSF) ApoE, Clu, ApoA1, and CSF amyloid beta1-42 (Aß42) and tau levels were assessed in 403 individuals with subjective cognitive decline and mild cognitive impairment using enzyme-linked immunosorbent assay. Whether CSF apolipoprotein levels mediated APOEε4 allele frequency effects on CSF Aß42 and tau in nondemented elderly was investigated using mediation analysis, with age- and gender-adjusted linear regression analyses. CSF ApoE mediated 48% of the association between APOEε4 and CSF tau, whereas Clu and ApoA1 did not. In addition, CSF Clu partially mediated the relation between CSF ApoE and tau (12%). CSF apolipoproteins did not mediate the inverse relation between APOEε4 and CSF Aß42, despite a strong association between the latter 2 biomarkers. In summary, our findings suggest that ApoE and Clu are involved in Aß-independent pathways as part of the cascade leading to Alzheimer pathology.


Assuntos
Apolipoproteínas E/líquido cefalorraquidiano , Apolipoproteínas E/genética , Encéfalo/metabolismo , Clusterina/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Genótipo , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteína A-I/líquido cefalorraquidiano , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano
19.
J Neurol ; 266(7): 1685-1692, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30963253

RESUMO

BACKGROUND: Atypical cerebrospinal fluid (CSF) patterns, involving an increase in the concentration of phosphorylated-tau (P-tau) proteins but normal amyloid-ß concentration, are not uncommon in patients with mild neurocognitive disorders and suspected Alzheimer's disease (AD). In these conditions, however, AD diagnosis may be ruled out in the absence of any amyloid deposition at positron-emission tomography (PET). This pilot cross-sectional study was aimed to determine whether this negativity of amyloid PET can be predicted by CSF profiles in such patients. METHODS: Twenty-five patients (73 [68-80] years, 10 women) with mild neurocognitive disorders, suspected AD and an increase in the CSF concentration of P-tau proteins but normal Aß42 concentration and Aß42/Aß40 ratio were prospectively included and referred to a 18F-florbetaben PET. The latter was considered as definitively negative with the conjunction of both visual (brain amyloid plaque load score) and quantified (standard uptake value ratios) criteria. Predictors of a negative PET were searched among current CSF biomarkers (Aß42, Aß40, T-tau, P-tau, Aß42/Aß40, Aß42/p-tau). RESULTS: Amyloid PET was negative in 15 patients (60%) with a CSF Aß42 concentration being the sole independent predictor of this negativity. The criterion of an Aß42 concentration in the very high range (> 843 pg/mL), observed in 60% (15/25) of the study patients, was associated with a negative amyloid PET in 93% (14/15) of cases. CONCLUSIONS: In mild neurocognitive disorders patients with suspected AD and showing an increase in CSF P-tau protein level, amyloid PETs are commonly negative, when Aß42 concentration is in the very high range. In such case, AD diagnosis based on biomarkers can be ruled out with reasonable certainty, without the need for additional CSF second-line assays or results from amyloid PET.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons/métodos , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Feminino , Humanos , Masculino , Fragmentos de Peptídeos/metabolismo , Fosforilação/fisiologia , Projetos Piloto , Estudos Prospectivos , Proteínas tau/metabolismo
20.
Neuroreport ; 30(8): 586-591, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-30964766

RESUMO

This study aimed to identify the change of cerebrospinal fluid (CSF) zinc-α2-glycoprotein (ZAG), tau protein and phosphorylated tau 181 (P-Tau 181), and analyze their association with white matter impairment (WMI) in patients with temporal lobe epilepsy (TLE). Levels of ZAG, tau, and P-Tau 181 in CSF were measured by enzyme-linked immunosorbent assay. WMI was scored based on Scheltens and Ylikoski scales. ZAG and total tau (T-Tau) were decreased in CSF of patients with TLE than controls (P<0.05 and 0.01, respectively), but P-Tau 181 showed no statistical difference. P-Tau 181/T-Tau ratio was increased in CSF of patients with TLE than controls (P<0.01). Patients with TLE have severer WMIs than controls (P<0.01). Linear by linear association analysis showed a correlation between WMI and TLE (P<0.01), Spearman's correlation analysis showed a correlation between T-Tau, P-Tau 181/T-Tau ratio and scores of WMIs (P<0.01). Receiver operating curves indicated apparent diagnostic value of T-Tau and P-Tau 181/T-Tau ratio in differentiating patients with TLE from controls (area under curve=1 and 0.936, respectively). ZAG also showed a lower but favorable diagnostic value (area under curve=0.771). ZAG, T-Tau, and P-Tau 181/T-Tau ratio in CSF may be potential biomarkers of WMI of TLE if further researched, and these findings may also be involved in potential mechanism of brain damage in TLE.


Assuntos
Epilepsia do Lobo Temporal/líquido cefalorraquidiano , Epilepsia do Lobo Temporal/patologia , Proteínas de Plasma Seminal/líquido cefalorraquidiano , Substância Branca/patologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Biomarcadores/líquido cefalorraquidiano , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
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