Publications by authors named "Aline Dorey"

6 Publications

  • Page 1 of 1

Cerebrospinal Fluid Aβ40 Improves the Interpretation of Aβ42 Concentration for Diagnosing Alzheimer's Disease.

Front Neurol 2015 27;6:247. Epub 2015 Nov 27.

Neurochemistry Unit, Biochemistry Department, Hospices Civils de Lyon, Groupement Hospitalier Est , Bron , France ; BioRaN Team, Lyon Neuroscience Research Center, CNRS UMR 5292, INSERM U1028, Lyon 1 University , Bron , France.

The combination of decreased amyloid β42 (Aβ42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer's disease (AD). Previous studies showed significant heterogeneity in CSF Aβ42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide β42/β40 ratio has better diagnostic performance than Aβ42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid β40 peptide (Aβ40) for biological diagnosis of AD when CSF Aβ42 levels failed. CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau ≥ 400 ng/L, P-Tau181 ≥ 60 ng/L, and Aβ42 ≤ 700 ng/L. CSF Aβ40 was assayed in AD patients with CSF Aβ42 levels above 700 ng/L and non-AD patients with CSF Aβ42 levels below 700 ng/L. CSF Aβ40 levels were higher in AD than non-AD patients. The receiver operator characteristic curves of CSF Aβ40 and the Aβ42/Aβ40 ratio defined AD cut-off values at 12,644 ng/L and 0.06, respectively. In AD patients with non-pathological CSF Aβ42, CSF Aβ40 concentration was able to correct 76.2% of cases when expressed as CSF Aβ42/Aβ40 ratio and 94.7% of cases when used alone. Using CSF Aβ42 and then CSF Aβ40, the percentage of misinterpreted AD patients fell to 1.0%. CSF Aβ40 concentration improved interpretation of Aβ42 level for the diagnosis of AD. CSF Aβ40 alone showed better diagnostic performance than the amyloid peptide Aβ42/Aβ40 ratio. The added value of determining CSF Aβ40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers.
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December 2015

The workflow from post-mortem human brain sampling to cell microdissection: a Brain Net Europe study.

J Neural Transm (Vienna) 2015 Jul 16;122(7):975-91. Epub 2015 May 16.

INSERM U1028; CNRS UM5292; Lyon Neuroscience Research Center, Neuro-oncology and Neuro-inflammation Team, 69000, Lyon, France,

Brain banks manage and store fully clinically and pathologically characterised brains. The diversity of techniques used in research projects increases. These biological resource centres are made to adapt brain tissue processing. Furthermore, the development of more sensitive techniques to analyse nucleic acids and proteins offers new fields of exploration when combined with laser capture microdissection in order to decipher the physiopathology of diseases at the cell level. In this study, our goal was to evaluate procedures and set a workflow compatible with the constraints of brain banks, from brain sampling to laser capture microdissection and pre-analytical quality assessment. We compared various methods of freezing brain tissue, focused on morphological quality preservation of brain microscopical structures and on the quality of nucleic acid or protein yields. Staining protocols combined with strategies to lower neurones autofluorescence were adapted for the same purpose. Finally, we found that laser capture microdissection is possible in the setting of brain banks. However, the entire process has to be envisioned from the autopsy to the analysis. The impact on protein or nucleic acid quality is a limitation that restricts the amount of samples available for this purpose.
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July 2015

Association of cerebrospinal fluid prion protein levels and the distinction between Alzheimer disease and Creutzfeldt-Jakob disease.

JAMA Neurol 2015 Mar;72(3):267-75

Hospices Civils de Lyon, Groupement Hospitalier Est, Department of Biochemistry, Neurochemistry Unit, Lyon, France6Lyon 1 University, Lyon Neuroscience Research Center, Bron Cedex, France.

Importance: Although typical forms of Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypes may pose a diagnostic challenge. The major biological diagnostic biomarker for identifying CJD, 14-3-3 protein in cerebrospinal fluid (CSF), unfortunately lacks specificity when confronting a rapid dementia presentation.

Objective: To assess the relevance of total CSF prion protein (t-PrP) levels in the differential biological diagnosis between atypical AD phenotypes and CJD.

Design, Setting, And Participants: A retrospective study in an autopsy-confirmed cohort of 82 patients was performed to evaluate the relevance of CSF t-PrP to distinguish 30 definite cases of AD from 52 definite cases of CJD. Next, CSF t-PrP concentration was measured in a cohort of 104 patients including 55 patients with probable AD, 26 with probable sporadic CJD, and 23 control patients for whom 14-3-3 protein, total tau, phosphorylated tau 181 (P-tau181), and Aβ1-42 were available. We investigated 46 patients diagnosed as having probable AD who presented atypical phenotypes. A diagnosis strategy was proposed to classify atypical AD phenotypes with suspicion of CJD based on a decision tree combining CSF biomarkers.

Main Outcomes And Measures: We determined CSF t-PrP levels for all patients. We calculated the ratio of total tau and P-tau181 and determined the diagnostic accuracy of each biomarker alone or in combination. We calculated the misclassification rate for each biomarker that corresponded to the percentage of patients within the group of atypical AD phenotypes wrongly classified as CJD.

Results: In patients with CJD, CSF t-PrP concentrations were decreased compared with control participants and patients with AD. When considering the differential diagnosis of CJD compared with atypical AD phenotypes, CSF t-PrP determination reached 82.1% sensitivity and 91.3% specificity. The misclassification rate of atypical AD phenotypes decreased from 43.5%, obtained when using the CSF 14-3-3 protein determination alone, to only 4.3% when calculating the ratio total tau/(P-tau181 × t-PrP). The proposed classification tree permitted correct classification of 98.4% of the patients.

Conclusions And Relevance: For unusual phenotypes of AD, especially cases presenting with a biological ambiguity suggesting CJD, determination of CSF t-PrP levels increased diagnostic accuracy. The use of CSF t-PrP levels may be beneficial in clinical practice in addition to the current classic biomarkers.
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March 2015

Risk factors of caregiver burden among patients with Alzheimer's disease or related disorders: a cross-sectional study.

J Alzheimers Dis 2015 ;44(3):907-16

Memory Research Centre of Lyon (CMRR); Geriatrics Unit, Charpennes Hospital, University Hospital of Lyon, Villeurbanne, France Research Clinic Centre (CRC) - VCF (Aging - Brain - Frailty), Charpennes Hospital, University Hospital of Lyon, Villeurbanne, France University Lyon 1, INSERM, U1028, UMR CNRS 5292, Research Centre of Neurosciences of Lyon, Lyon, France.

Background: Caregivers play a major role in the care of patients with dementia and are themselves at higher risk of disease.

Objectives: We investigate which factors are associated with caregivers burden of outpatients visiting a memory clinic and how functional autonomy and behavioral and psychological symptoms can influence caregiver burden.

Methods: The study population was chosen from outpatients with progressive cognitive complaint. The caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The relationship was assessed between the ZBI and the patients characteristics, including Neuropsychiatric Inventory (NPI), Instrumental Activities of Daily Living scale (IADL), the Mini-Mental State Examination (MMSE), etiology, and stage of the cognitive impairment.

Results: In a population of 548 patients, IADL, NPI, antidepressant drugs, and MMSE were found to be related to ZBI, while diagnosed etiology and disease stage were not significant: ZBI decreased by 0.34 point for every unit of IADL, and by 0.03 point for every unit of MMSE; ZBI increased by 0.03 point for every unit of NPI. From the IADL scale, the ability to handle finances, food preparation, responsibility to take medications, mode of transportation, and ability to use the telephone increased the ZBI. Five areas of the NPI increased the ZBI: apathy, agitation, aberrant motor behavior, appetite disorders (p < 0.001), and irritability (p = 0.03).

Conclusion: Caregivers experience a higher burden due to disease symptoms such as impairment of functional autonomy and behavioral and cognitive impairment, whatever the etiology of the cognitive decline.
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October 2015

Initial memory deficit profiles in patients with a cerebrospinal fluid Alzheimer's disease signature.

J Alzheimers Dis 2014 ;41(4):1109-16

Research and Resources Memory Center of Lyon, Hôpital des Charpennes, Hospices Civils de Lyon, Lyon, France University Lyon I, Lyon, France INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Lyon, France.

Background: Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown.

Objective: The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD.

Methods: Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Three different memory profiles were identified according to the results of FCSRT.

Results: The median age was 72 year-old [interquartiles: 65-76]. The median MMSE score was 23 [interquartiles: 21-25]. 88% of the patients (n = 64) presented with a medial temporal amnesia profile. The dysexecutive amnesia and normal verbal episodic memory profiles represented respectively 5% (n = 4) and 7% (n = 5). There were no significant differences in term of age, gender, and MMSE score between the three profile groups.

Conclusion: In a population initially presenting with memory complaints and depicting a CSF AD signature, a high proportion of medial temporal amnesia is disclosed as expected, but also a proportion of dysexecutive amnesia and normal FCSRT.
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March 2015

Impact of harmonization of collection tubes on Alzheimer's disease diagnosis.

Alzheimers Dement 2014 Oct 23;10(5 Suppl):S390-S394.e2. Epub 2013 Oct 23.

Service de Neurobiologie, Hospices Civils de Lyon, Université Lyon 1-CNRS UMR5292-INSERM U1028, Lyon, France.

Objective: The objective of this study was to analyze differences in biomarker outcomes before and after harmonization of cerebrospinal fluid (CSF) collection tubes in Alzheimer's disease (AD) diagnosis.

Methods: We analyzed data from French memory centers that switched from different CSF collection tubes to a common one. A total of 1966 patients were included in the study. CSF concentrations of β-amyloid 1-42 (Aβ42), total tau, and phosphorylated tau (p-tau181) were measured in each center using the same commercial enzyme-linked immunoabsorbent assay (ELISA) kits. The diagnostic value of CSF biomarkers according to the type of tube used was then assessed using different cutoffs.

Results: The predictive value of Aβ42 was highly affected by the type of collection tube used. The optimal cutoff value for p-tau181 appeared not to be affected by the type of collection tube whereas that of total tau was slightly changed. New optimal cutoff values were then computed.

Conclusions: In a routine clinical environment, the selection of the collection tube and biomarker cutoff value makes a major difference in AD biological diagnosis. The use of a common collection tube among different centers will reduce the risk of misdiagnosis and incorrect patient stratification.
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October 2014