Cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer’s disease

Magalhães, Cíntia Lopes de Brito; Figueiró, Micheli; Fraga, Vanêssa Gomes; Mateo, Elvis Cueva; Toledo, Andre; Carvalho, Maria das Graças; Caramelli, Paulo; Gomes, Karina Braga

doi:10.5935/1676-2444.20150059

Cited by 9 publications

(6 citation statements)

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“…Although t‐tau has been considered a marker of gross neurodegeneration and axonal atrophy, some observations do not fit with this interpretation. For example, t‐tau elevations appear to be relatively specific to AD; t‐tau concentrations are typically lower in patients with other neurodegenerative diseases, such as Parkinson's disease dementia, Lewy body dementia, and progressive supranuclear palsy [37–41]. Of course, this is not always the case: tau is elevated in Creutzfeldt‐Jakob disease, adding further complexity to the role of t‐tau in neurodegeneration [42].…”

Section: Discussionmentioning

confidence: 99%

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Vogt

Norton

Jonaitis

et al. 2019

A&D Transl Res & Clin Interv

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Introduction Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t-tau and alternative biomarkers of neurodegeneration—neurogranin and neurofilament light protein (NFL)—add value in predicting subclinical cognitive decline. Methods One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t-tau. Models were compared using likelihood ratio tests. Results Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t-tau did not. Discussion These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Vogt

Norton

Jonaitis

et al. 2019

A&D Transl Res & Clin Interv

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“…In addition, 10 out of the 14 patients had their CSF analyzed for amyloid beta 42 (Aβ 42), total tau (ttau) and phosphorylated tau (p-tau). CSF samples were collected by lumbar puncture and biomarkers were measured with a double-sandwich enzyme-linked immunosorbent assay (ELISA) kit (Innogenetics, Gent, Belgium), as previously described (Magalhães et al, 2015). Patients with marked cerebrovascular lesions on brain MRI (Fazekas grade 3) were not included.…”

Section: Participantsmentioning

confidence: 99%

Circulating Angiotensin-(1–7) Is Reduced in Alzheimer’s Disease Patients and Correlates With White Matter Abnormalities: Results From a Pilot Study

et al. 2021

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IntroductionAlzheimer’s disease (AD) is the leading cause of dementia worldwide. Despite the extensive research, its pathophysiology remains largely unelucidated. Currently, more attention is being given to the disease’s vascular and inflammatory aspects. In this context, the renin-angiotensin system (RAS) emerges as a credible player in AD pathogenesis. The RAS has multiple physiological functions, conducted by its two opposing axes: the classical, led by Angiotensin II (Ang II), and the alternative, driven by Angiotensin-(1–7) [Ang-(1–7)]. These peptides were shown to interact with AD pathology in animal studies, but evidence from humans is scarce. Only 20 studies dosed RAS molecules in AD patients’ bloodstream, none of which assessed both axes simultaneously. Therefore, we conducted a cross-sectional, case-control exploratory study to compare plasma levels of Ang II and Ang-(1–7) in AD patients vs. age-matched controls. Within each group, we searched for correlations between RAS biomarkers and measures from magnetic resonance imaging (MRI).MethodsWe evaluated patients with AD (n = 14) and aged-matched controls (n = 14). Plasma Ang II and Ang-(1–7) were dosed using ELISA. Brain MRI was performed in a 3 Tesla scan, and a three-dimensional T1-weighted volumetric sequence was obtained. Images were then processed by FreeSurfer to calculate: (1) white matter hypointensities (WMH) volume; (2) volumes of hippocampus, medial temporal cortex, and precuneus. Statistical analyses used non-parametrical tests (Mann-Whitney and Spearman).ResultsAng-(1–7) levels in plasma were significantly lower in the AD patients than in controls [median (25th–75th percentiles)]: AD [101.5 (62.43–126.4)] vs. controls [209.3 (72–419.1)], p = 0.014. There was no significant difference in circulating Ang II. In the AD patients, but not in controls, there was a positive and significant correlation between Ang-(1–7) values and WMH volumes (Spearman’s rho = 0.56, p = 0.038). Ang-(1–7) did not correlate with cortical volumes in AD or in controls. Ang II did not correlate with any MRI variable in none of the groups.ConclusionIf confirmed, our results strengthen the hypothesis that RAS alternative axis is downregulated in AD, and points to a possible interaction between Ang-(1–7) and cerebrovascular lesions in AD.

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“…A subset of patients (eight AD and eight bvFTD) underwent lumbar puncture for cerebrospinal fluid (CSF) biomarkers (Aß42, Tau and P-Tau) analyses. For this subgroup, all AD patients had an "AD CSF biomarker profile", defined by Tau/Aß42 > 0.52 (Magalhães et al, 2015). None of the bvFTD patients had this biomarker profile.…”

Section: Introductionmentioning

confidence: 99%

Disinhibition in Frontotemporal Dementia and Alzheimer’s Disease: A Neuropsychological and Behavioural Investigation

Mariano

O’Callaghan

Guimarães

et al. 2019

J Int Neuropsychol Soc

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Objective:Cognitive tests of inhibitory control show variable results for the differential diagnosis between behavioural variant of Frontotemporal Dementia (bvFTD) and Alzheimer’s disease (AD). We compared the diagnostic accuracies of tests of inhibitory control and of a behavioural questionnaire, to distinguish bvFTD from AD.Methods:Three groups of participants were enrolled: 27 bvFTD patients, 25 AD patients, and 24 healthy controls. Groups were matched for gender, education, and socio-economic level. Participants underwent a comprehensive neuropsychological assessment of inhibitory control, including Hayling Test, Stroop, the Five Digits Test (FDT) and the Delay Discounting Task (DDT). Caregivers completed the Barratt Impulsiveness Scale 11th version (BIS-11).Results:bvFTD and AD groups showed no difference in the tasks of inhibitory control, while the caregiver questionnaire revealed that bvFTD patients were significantly more impulsive (BIS-11: bvFTD 76.1+9.5, AD 62.9+13, p < .001).Conclusions:Neuropsychological tests of inhibitory control failed to distinguish bvFTD from AD. On the contrary, impulsivity caregiver-completed questionnaire provided good distinction between bvFTD and AD. These results highlight the current limits of cognitive measures of inhibitory control for the differential diagnosis between bvFTD and AD, whereas questionnaire information appears more reliable and in line with clinical diagnostics.

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Cerebrospinal fluid biomarkers for the differential diagnosis of Alzheimer’s disease

Cited by 9 publications

References 0 publications

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Circulating Angiotensin-(1–7) Is Reduced in Alzheimer’s Disease Patients and Correlates With White Matter Abnormalities: Results From a Pilot Study

Disinhibition in Frontotemporal Dementia and Alzheimer’s Disease: A Neuropsychological and Behavioural Investigation

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