Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders

Paquet, Claire; Bouaziz‐Amar, Elodie; Cognat, Emmanuel; Volpe‐Gillot, Lisette; Haddad, Victor; Mahieux, Florence; Dekimeche, Siham; Defontaines, Bénédicte; Chabriat, Hugues; Belin, Cathérine; Texeira, Antonio; Goutagny, Stéphane; Questel, Frank; Azuar, Julien; Sellier, Pierre‐Olivier; Laplanche, Jean‐Louis; Hugon, Jacques; Dumurgier, Julien

doi:10.3233/jad-180240

Cited by 9 publications

(11 citation statements)

References 38 publications

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“…Gender distribution was equal across groups independent of classification used (by Aβ1-42 and cognitive status or biomarker only). A tendency towards higher representation of male subjects in the A+/T-vs the A+/T+ group was observed which was in line with earlier reports (Paquet et al, 2018). Participants classified as pAD and A+/T+ had lower weight and BMI and participants classified as A−/T− were younger.…”

Section: Demographic Biomarker and Cognitive Characteristicssupporting

confidence: 91%

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Timmers

Tesseur

Bogert

et al. 2019

Neurobiology of Aging

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Amyloid β (Aβ) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aβ and tau for cognitive impairment in early AD was examined with crosssectional analysis, measured by cerebrospinal fluid (CSF) biomarkers (Aβ1-42, 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 (Aβ−), mild cognitively impaired (Aβ−), preclinical AD (Aβ+), and prodromal AD (Aβ+). Overall, cognitive impairment (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 Aβ status, this correlation to t-tau was applicable only in Aβ+ participants (n=139; r=−0.451, p<0.001) but not Aβ− participants (n=107; r=0.137, p=0.16), with identical findings for p-tau. Both tau (p<0.0001) and interaction of Aβ1-42 with tau (p=0.006) affected RBANS, but not Aβ1-42 alone. Cognitive/memory performance correlated well with CSF tau levels across early stages of AD, although the correlation is Aβ dependent.

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Section: Demographic Biomarker and Cognitive Characteristicssupporting

confidence: 91%

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Timmers

Tesseur

Bogert

et al. 2019

Neurobiology of Aging

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“…In this study we chose not to use the recently proposed A/T/N classification[18, 28] as we have previously showed that some profiles (A-T+N-, A+T+N-) were quite rare, representing less than 1% of the sample [25]. Furthermore, in our data CSF Tau and CSF p-Tau 181 were highly correlated (Spearman coefficient correlation = 0.84, P<0.001).…”

Section: Methodsmentioning

confidence: 63%

“…For the present study, CSF biomarkers from 18 hospitals in and around Paris, France, were aggregated in one biochemistry department. All patients seen between January 1 st 2008 and January 1 st 2018 for whom AD biomarkers from CSF were available were included in the analysis; methods and characteristics of the population have been previously reported elsewhere [25, 26]. The study was approved by the Ethical Committee of Paris University Hospitals.…”

Section: Methodsmentioning

confidence: 99%

Biomarker profiles of Alzheimer’s disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau

et al. 2019

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Objective To investigate the relationship between cerebrospinal fluid (CSF) β-amyloid peptide (Aβ42) and CSF Tau in a large population of patients referred to memory clinics for investigation of cognitive dysfunction. Methods We analyzed Alzheimer’s disease (AD) biomarkers in CSF taken from 3565 patients referred to 18 French memory clinics. Patients were classified into four profiles according to levels of CSF biomarkers (A: amyloidosis, N: neurodegeneration). The association between CSF Tau and CSF Aβ42 were analyzed using general linear regression models, in the overall population and stratified by biomarkers profiles. We compared linear and quadratic models using Akaike information criterion. We also assessed change in biomarker profiles in a subset of patients who had 2 assessments of biomarkers. Results CSF Tau was negatively associated with CSF Aβ42 in the overall population, following a non-linear quadratic model. However, the nature of this association was different in the 4 profiles: positive association in A-N- profile, negative association in A-N+ and A+N+ profiles, lack of association in A+N- patients. When considering patients with longitudinal data on profiles, 36% of those initially classified as A-N+ evolved to an A+N+ profile. Conclusions The nature of the association between CSF Aβ42 and CFS Tau depends on the A/N profiles of patients. These results suggest an increase in CSF Aβ42 early in the disease before its decline while tau pathology progresses, this pattern is particularly observed in non-APOE4 subjects. This phenomenon may explain why some patients with neurodegeneration only markers convert to an AD profile (A+N+) over time.

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“…Within SNAP cases, few studies distinguished A−T+N+ from A+T-N+. A recent survey from a large AD biomarker database showed that 64% of A−N+ cases were T+ [59] . However, this study used high T-tau to define N+, leaving out N+ patients determined by neuroimaging (where atrophy and/or hypometabolism define N+).…”

Section: Discussionmentioning

confidence: 99%

Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ_42/40 ratio

Pouclet‐Courtemanche

Nguyen

Skrobala³

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Patients with positive tauopathy but negative Aβ 42 (A−T+) in the cerebrospinal fluid (CSF) represent a diagnostic challenge. The Aβ 42/40 ratio supersedes Aβ 42 and reintegrates “false” A−T+ patients into the Alzheimer's disease spectrum. However, the biomarker and clinical characteristics of “true” and “false” A−T+ patients remain elusive. Methods Among the 509 T+N+ patients extracted from the databases of three memory clinics, we analyzed T+N+ patients with normal Aβ 42 and compared “false” A−T+ with abnormal Aβ 42/40 ratio and “true” A−T+ patients with normal Aβ 42/40 ratio, before CSF analysis and at follow-up. Results 24.9% of T+N+ patients had normal Aβ 42 levels. Among them, 42.7% were “true” A−T+. “True” A−T+ had lower CSF tau P181 than “false” A−T+ patients. 48.0% of “true” A−T+ patients were diagnosed with frontotemporal lobar degeneration before CSF analysis and 64.0% at follow-up, as compared with 6% in the “false” A−T+ group ( P < .0001). Discussion Frontotemporal lobar degeneration is probably the main cause of “true” A−T+ profiles.

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Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders

Cited by 9 publications

References 38 publications

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Biomarker profiles of Alzheimer’s disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau

Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ_42/40 ratio

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Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders

Cited by 9 publications

References 38 publications

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease

Biomarker profiles of Alzheimer’s disease and dynamic of the association between cerebrospinal fluid levels of β-amyloid peptide and tau

Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ42/40 ratio

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Frontotemporal dementia is the leading cause of “true” A−/T+ profiles defined with Aβ_42/40 ratio