CSF biomarkers and amyloid PET: concordance and diagnostic accuracy in a MCI cohort

Spallazzi, Marco; Barocco, Federica; Michelini, Giovanni; Immovilli, Paolo; Taga, Arens; Morelli, Nicola; Ruffini, Livia; Caffarra, Paolo

doi:10.1007/s13760-019-01112-8

Cited by 24 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the NIA-AA research framework suggests that either CSF or amyloid PET enables to determine one’s biological AD profile, in some cases, CSF Aβ 1 – 42 might become abnormal before amyloid PET (Bateman et al, 2012; Ben Bouallegue et al, 2017). Based on these evidence, some previous studies suggested that the combination of amyloid CSF and PET biomarker may further improve the accuracy of biological classification to some extent (Bouter et al, 2019; Spallazzi et al, 2019). Thus, we adopted the recommended composite Florbetapir cutoff value of 1.11 (whole cerebellum as reference region) (i.e., A+ represents amyloid PET SUVR composite score > 1.11), which is equivalent to the upper 95% confidence interval above the mean of a group of young healthy controls (Landau et al, 2013).…”

Section: Methodsmentioning

confidence: 92%

Application of T1-/T2-Weighted Ratio Mapping to Elucidate Intracortical Demyelination Process in the Alzheimer’s Disease Continuum

Luo

Zeng

et al. 2019

Front. Neurosci.

View full text Add to dashboard Cite

Background The biological diagnosis criteria of the Alzheimer’s disease (AD) suggests that previous work may misclassify the cognitive impairment caused by other factors into AD. Consequently, re-assessing the imaging profile of AD continuum is needed. Considering the high vulnerability of cortical association fibers, we aimed to elucidate the cortical demyelination process in the AD continuum biologically defined.Methods According to the biological diagnosis criteria, we determined the positive amyloid status (A+) as cerebrospinal fluid (CSF) amyloid1–42 < 192 pg/ml, Florbetapir Positron emission tomography (PET) composite standardized uptake value ratio (SUVR) >1.11. Also, the positive Tau status (T+) was determined as p-Tau181 > 23 pg/ml. Based on the cognitive characterization, we further categorized 252 subjects into 27 cognitively unimpaired with normal AD biomarkers (A−T−, controls), 49 preclinical AD (A+T+), 113 AD with mild cognitive impairment (MCI) (A+T+), and 63 AD dementia (A+T+). We estimated the intracortical myelin content used the T1- and T2-weighted (T1W/T2W) ratio mapping. To investigate the sensitivity of the ratio mapping, we also utilized well-validated AD imaging biomarkers as the reference, including gray matter volume and Fludeoxyglucose PET (FDG-PET). Based on the general linear model, we conducted the voxel-wise two-sample T-tests between the controls and each group in the AD continuum.Results Compared to the controls, the results showed that the preclinical AD patients exhibited decreased T1W/T2W ratio value in the right inferior parietal lobule (IPL); as the disease progresses, the prodromal AD patients demonstrated lower ratio value in bilateral IPL, with hippocampus (HP) atrophy. Lastly, the AD dementia patients exhibited decreased ratio value in bilateral IPL and hippocampus; also, we observed the bilateral temporal cortices atrophy and widespread decreased metabolism in the AD dementia patients. After corrected with gray volume, the results remained mostly unchanged.Conclusion Our study implied the decreased right IPL T1W/T2W ratio might represent early AD-related demyelination in disease continuum. Additionally, we demonstrated that the T1W/T2W ratio mapping is an easy-to-implement and sensitive metric to assess the intracortical myelin content in AD, particularly in the early stage.

show abstract

Section: Methodsmentioning

confidence: 92%

Application of T1-/T2-Weighted Ratio Mapping to Elucidate Intracortical Demyelination Process in the Alzheimer’s Disease Continuum

Luo

Zeng

et al. 2019

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Levels of baseline CSF beta‐amyloid 1–42 (Aβ 42 ), total tau protein (t‐tau) and phosphorylated tau (p‐tau) were measured by commercially available enzyme‐linked immunosorbent assay (ELISA) kits (Innogenetics ® , Ghent, Belgium) and expressed in nanograms per litre (ng/L). We considered Aβ 42 values <600 ng/L and p‐tau/Aβ 42 ratio >0.13 as pathological, 19,20 and suggestive for an “A+” and “A+/T+” status, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…After acquisition of written informed consent, lumbar puncture was performed at the patient's bedside. CSF samples were collected in sterile polypropylene tubes and analysed in the local Department of Laboratory 19,20 and suggestive for an "A+" and "A+/T+" status, respectively.…”

Section: Csf Acquisition and Analysismentioning

confidence: 99%

Plasma neurofilament light chain levels and cognitive testing as predictors of fast progression in Alzheimer’s disease

Santangelo

Masi

Spinelli

et al. 2021

Euro J of Neurology

View full text Add to dashboard Cite

Background: Alzheimer's disease (AD) is characterized by a heterogeneous course.Predicting a fast rather than a slow decline over time is crucial to both provide a reliable prognosis and elaborate stricter enrolment criteria in clinical trials. Here we searched for independent predictors of cognitive decline rate to assess the risk of fast disease progression already at baseline. Methods: Fifty-three subjects with an "in-vivo biomarker confirmed" diagnosis of AD were included. Neuropsychological assessment, plasma neurofilaments (NfL) concentrations and, in a subsample of 23 patients, brain magnetic resonance imaging were available.Patients were labelled FAST or SLOW depending on the Mini-Mental State Examination (MMSE) points lost per year (FAST if more than 3 points). We adopted single logistic regression models to search for independent predictors of FAST progression.Results: At baseline no differences were found between FAST and SLOW subgroups in demographics, MMSE scores, vascular burden and medial temporal lobe atrophy measurements. Higher plasma NfL concentrations and worse scores at semantic verbal fluency (SVF) and clock drawing test (CDT) were independent predictors of FAST decline, after controlling for age, education, sex and baseline disease severity stage. The regression model combining all the predictors correctly classified 80% of patients overall. The risk of FAST decline was 81.2% if all the three predictors were abnormal (i.e., SVF ≤21.5, CDT ≤5.5, NfL ≥22.19).Conclusions: An easily applicable algorithm, including plasma NfL measurement and two neuropsychological tests worldwide adopted in clinical practice (SVF and CDT), may allow clinicians to reliably stratify AD patients in relation to the risk of fast cognitive decline.

show abstract

“…Clinical characteristics, neurocognitive tests, positron emission tomography (PET) and magnetic resonance imaging (MRI) can diagnose aMCI but they are time consuming 12 . Amyloid PET with different probes ( 18 F-utemetamol and 18 F-orbetapir, et al) are available to precisely detect and monitor brain amyloid deposition in MCI patients but costliness 13,14 . Longitudinal studies showed that amyloid-positive MCI subjects have greater cognitive deterioration than amyloid-negative subjects 15,16 .…”

Section: Read Full Licensementioning

confidence: 99%

Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1

Yang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Amnestic mild cognitive impairment (aMCI) is a prodromal stage of Alzheimer’s disease with the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) imbalance. Altered microRNAs (miRNA) associated with BACE1 may be potential biomarkers for aMCI diagnosis. The aims of this study were to find an effective diagnostic model for aMCI, and to explore the modulation of candidate miRNAs on BACE1 expression.Methods: Plasma RNA was extracted from participants enrolled in China longitudinal aging study (CLAS). MiRNA profiling was performed using microarray sequencing on a discovery set, compromising five aMCI subjects that confirmed by 18F-Flutemetamol PET scan and five normal controls (NC). Quantitative reverse transcription PCR was used to validate the expression levels of differently expressed miRNAs on an analysis set (20 aMCI subjects and 10 NC). Diagnostic capability of candidate miRNAs was assessed in a validation set (40 aMCI subjects and 40 NC). Modulation of candidate miRNAs on BACE1 was explored in rat and human hippocampal neurons in vitro through transfection of miRNA mimics or inhibitor lentivirus.Results: In discovery set, we verified 46 significantly differentially expressed miRNAs between aMCI and NC groups (P<0.05). Among these, 33 miRNAs were down-regulated and 13 miRNAs were up-regulated. In analysis set, miR-1185-2-3p, miR-1909-3p, miR-22-5p, and miR-134-3p also significantly decreased in aMCI group. Four miRNAs above and miR-107 which was found to decline in previous study were selected as potential biomarkers. A diagnostic model consists of five miRNAs above had an outstanding diagnostic accuracy (81.25%) to diagnose aMCI. Except for miR-134-3p, other four miRNAs modulated BACE1 expression and C-terminal fragments-beta production effectively in rat hippocampal neurons in vitro. Similar modulation of miR-1185-2-3p and miR-1909-3p were confirmed in human hippocampal neurons in vitro.Conclusion: A diagnostic model consists of five plasma miRNAs could be novel biomarker for aMCI diagnosis. These miRNAs might be involved in pathogenesis of AD through regulating expression of BACE1.

show abstract

CSF biomarkers and amyloid PET: concordance and diagnostic accuracy in a MCI cohort

Cited by 24 publications

References 36 publications

Application of T1-/T2-Weighted Ratio Mapping to Elucidate Intracortical Demyelination Process in the Alzheimer’s Disease Continuum

Application of T1-/T2-Weighted Ratio Mapping to Elucidate Intracortical Demyelination Process in the Alzheimer’s Disease Continuum

Plasma neurofilament light chain levels and cognitive testing as predictors of fast progression in Alzheimer’s disease

Plasma miRNAs as Biomarkers for Amnestic Mild Cognitive Impairment and Modulation on BACE1

Contact Info

Product

Resources

About