ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker

Manzine, Patrícia Regina; Ettcheto, Miren; Cano, Amanda; Busquets, Oriol; Marcello, Elena; Pelucchi, Silvia; Luca, Mónica Di; Endres, Kristina; Olloquequi, Jordi; Camins, Antoni; Cominetti, Márcia Regina

doi:10.1016/j.biopha.2019.108661

Cited by 57 publications

(36 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In previous studies, we and others have shown that levels of membrane-bound ADAM10 are reduced in platelets of patients with AD compared to cognitively healthy individuals (15,16,18) and that this reduction correlated with patients' cognitive performance, as measured by the CDT (27) or MMSE (14) scores. Moreover, levels and platelet ADAM10 activity were shown to be increased throughout cognitively healthy aging, pointing to the possibility that ADAM10 might contribute to or is a prerequisite for cognitively healthy aging (28).…”

Section: Discussionmentioning

confidence: 69%

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

Monteiro

Oliveira

Manzine

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 69%

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

Monteiro

Oliveira

Manzine

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In previous studies, we and others have shown that levels of membrane-bound ADAM10 are reduced in platelets of patients with AD compared to cognitively healthy individuals [15,16,18] and that this reduction correlated with patients' cognitive performance, as measured by the CDT [26] or MMSE [14] scores. Moreover, levels and platelet ADAM10 activity were shown to be increased throughout cognitively healthy aging, pointing to the possibility that ADAM10 might contribute to or is a prerequisite for cognitively healthy aging [27].…”

Section: Discussionmentioning

confidence: 69%

“…As a membrane-bound protein, ADAM10 acts as a sheddase cleaving different substrates on the plasma membrane, including APP in neurons; hence, avoiding the production, accumulation and aggregation of neurotoxic βA peptide [12,13]. Platelet ADAM10 levels were demonstrated to be decreased in AD patients, compared to the levels of cognitively healthy controls [14][15][16][17][18], whereas its plasma levels were increased in MCI and AD [19]. These results are in line with most postmortem data that reveal an overall decrease of ADAM10 mRNA, protein, and/or activity in central nervous tissue of AD patients compared to age-matched controls [20].…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…This was also shown by knockdown of ADAM10 using RNAi (81). ADAM10 cleavage of APP in Alzheimer's disease has been extensively studied [and is reviewed in (82,83)]. The expansion of importance in breast cancer emphasizes the examination of ADAM10 cleavage of APP in other cancers.…”

Section: Breast Cancermentioning

confidence: 97%

Targeting ADAM10 in Cancer and Autoimmunity

2020

View full text Add to dashboard Cite

ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker

Cited by 57 publications

References 136 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

Targeting ADAM10 in Cancer and Autoimmunity

Contact Info

Product

Resources

About