Blood-based Biomarkers of Alzheimer’s Disease: The Long and Winding Road

Manzine, Patrícia Regina; Vatanabe, Izabela Pereira; Peron, Rafaela; Grigoli, Marina Mantellatto; Pedroso, Renata Valle; Nascimento, Carla Manuela Crispim; Cominetti, Márcia Regina

doi:10.2174/1381612826666200114105515

Cited by 20 publications

(17 citation statements)

References 196 publications

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“…Biomarkers for AD are highly needed in clinic, especially those based on samples of easy collection, such as blood [5,10]. Currently, validated AD biomarkers are represented by neuroimage measures and quanti cation of the βA peptide, t-tau and p-tau derived from CSF, both requiring speci c equipment or invasive procedures, respectively.…”

Section: Discussionmentioning

confidence: 99%

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ADAM10 Plasma Levels Predict Worsening in Cognition of Older Adults: A 3-Year Follow-Up Study

Monteiro

Oliveira

Manzine

et al. 2020

Preprint

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Background Blood-based biomarkers for Alzheimer’s disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau and phosphorylated tau in cerebrospinal fluid (CSF), however, they are not attractive for large-scale screening. Blood-based biomarkers will allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, we and other research groups have already described that the plasma and platelet levels of ADAM10 are higher or lower, respectively, in patients with AD, compared to those cognitively healthy. Methods This was a three-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS) and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson’s chi-square tests with Yates continuity correction, for categorical data. Longitudinal analyzes of changes in the MMSE score were performed using Linear Mixed-Effects modeling. Results Baseline MMSE score and ADAM10 values were significantly associated with MMSE score values on the follow-up assessment. When analyzing the interaction with time, having a normal MMSE at baseline and ADAM10 plasma levels presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the effect of ADAM10 plasma levels on decreasing MMSE score values on follow-up seems to be more pronounced in those with normal MMSE at baseline. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults. Conclusions Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.

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Section: Discussionmentioning

confidence: 99%

“…Even in non-disease situations, the exchange of molecules and proteins between CSF and blood is well reported, despite the limitation imposed by BBB [9]. In this regard, several blood-based AD biomarker candidates have been described, including the α-secretase ADAM10 [10].…”

Section: Introductionmentioning

confidence: 99%

ADAM10 Plasma Levels Predict Worsening in Cognition of Older Adults: A 3-Year Follow-Up Study

Monteiro

Oliveira

Manzine

et al. 2020

Preprint

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“…Several blood-based AD biomarker candidates have been described, including the ADAM10 [10], which is the main α-secretase participating in the nonamyloidogenic cleavage of APP in neurons, thus having a protective function against this dementia [11]. ADAM10 can be found in different isoforms, and we have already reported that the membrane-bound platelet ADAM10 is active cleaving a fluorogenic substrate, while the isoform found soluble in plasma and CSF is inactive [12].…”

Section: Introductionmentioning

confidence: 95%

ADAM10 plasma levels predict worsening in cognition of older adults: a 3-year follow-up study

et al. 2021

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Background Blood-based biomarkers for Alzheimer’s disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Blood-based biomarkers allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, in this study, we evaluated whether plasma ADAM10 levels would be predictors of declines in cognition in community-dwelling older adults after a 3-year period follow-up. Methods This was a 3-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS), and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson’s chi-square tests with Yates continuity correction for categorical data. Longitudinal analyzes of changes in the MMSE scores were performed using linear mixed-effects modeling. Results Baseline MMSE scores and ADAM10 levels were significantly associated with MMSE scores on the follow-up assessment. When analyzing the interaction with time, normal MMSE scores and the ADAM10 plasma levels at baseline presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the predictive effect of ADAM10 plasma levels on decreasing MMSE scores on follow-up seems to be more pronounced in participants with normal MMSE, when compared with those with altered MMSE scores at baseline. Conclusions Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.

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“…While CSF is considered an ideal source when it directly interacts with the extracellular space of the brain, CSF sampling is not trivial. There are trials of using peripheral blood to measure oxidative stress changes in neurodegenerative diseases 97‐99 . Therefore, direct comparison of such measurement between CSF and serum should be performed in future.…”

Section: Csf Oxidative Stress Markers In Ad In Vivomentioning

confidence: 99%

Cerebrospinal fluid oxidative stress markers in Alzheimer's disease

Sakakibara

Kawai

2020

Neurology & Clinical Neurosc

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Oxidative stress has a significant impact on neurodegenerative diseases. The present paper reviewed the role of oxidative stress in disease progression of Alzheimer's disease (AD) and measurement of the oxidative stress markers in cerebrospinal fluid (CSF) in AD in vivo. Oxidative stress measurement in CSF in AD provides knowledge of underlying pathophysiology, to be a counterpart of oxidative stress neuroimaging, and to help differentiating AD from other neurodegenerative diseases. In addition, these findings warrant future studies to see whether antioxidant intervention might help preventing progression of neurodegenerative diseases including AD.

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Blood-based Biomarkers of Alzheimer’s Disease: The Long and Winding Road

Cited by 20 publications

References 196 publications

ADAM10 Plasma Levels Predict Worsening in Cognition of Older Adults: A 3-Year Follow-Up Study

ADAM10 Plasma Levels Predict Worsening in Cognition of Older Adults: A 3-Year Follow-Up Study

ADAM10 plasma levels predict worsening in cognition of older adults: a 3-year follow-up study

Cerebrospinal fluid oxidative stress markers in Alzheimer's disease

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