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

Autor: Danielle dos Santos Maia Salheb de Oliveira, Henrique Pott-Junior, Grace Angélica de Oliveira Gomes, Maria Patrícia A. Oliveira Monteiro, Márcia Regina Cominetti, Marisa Silvana Zazzetta, Fabiana dos Santos Orlandi, Patricia Regina Manzine, Carla Manuela Crispim Nascimento, Ariene Angelini dos Santos Orlandi
Rok vydání: 2020
Předmět:
0301 basic medicine
medicine.medical_specialty
Neurology
Cognitive Neuroscience
tau Proteins
Disease
behavioral disciplines and activities
lcsh:RC346-429
lcsh:RC321-571
03 medical and health sciences
ADAM10 Protein
0302 clinical medicine
Cognition
Neuroimaging
Alzheimer Disease
Internal medicine
medicine
Dementia
Humans
Cognitive Dysfunction
Longitudinal Studies
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Yates's correction for continuity
lcsh:Neurology. Diseases of the nervous system
Aged
Amyloid beta-Peptides
business.industry
Research
ADAM10
Membrane Proteins
Biomarker
medicine.disease
Peptide Fragments
030104 developmental biology
Blood
Disease Progression
Biomarker (medicine)
Neurology (clinical)
Amyloid Precursor Protein Secretases
business
Alzheimer’s disease
030217 neurology & neurosurgery
Geriatric psychiatry
Biomarkers
Follow-Up Studies
Zdroj: Alzheimer's Research & Therapy
Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-8 (2021)
DOI: 10.21203/rs.3.rs-55336/v1
Popis: 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.
Databáze: OpenAIRE
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