ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer’s Disease

Abstract

ADAM10 is the main α-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of β-amyloid peptide (Aβ) in Alzheimer’s disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers.

Haplotype-Based Single-Step GWAS for Yearling Temperament in American Angus Cattle

“…Longevity is a productive trait that is affected to some degree by the cattle’s temperament, as aggressiveness is an undesirable trait and is a culling criterion in American Angus [ 53 ]. The ADAM metallopeptidase domain 10 ( ADAM10 ) gene was already identified as a biomarker for Alzheimer’s disease in humans, with functions related to the cleavage amyloid precursors that act during the inflammation process of senile plaques [ 54 ]. In cattle, ADAM10 was associated with tick resistance, with its importance in the inflammation process being the most likely reason [ 55 ].…”

Signature of miRNAs derived from the circulating exosomes of patients with amyotrophic lateral sclerosis

“…The regulation 10.3389/fnagi.2023.1106497 of ADAM10 by hsa-miR-1306 was demonstrated in SH-SY5Y cells expressing the 3'UTR of ADAM10 under a luciferase reporting vector (Augustin et al, 2012). ADAM10, an essential AD gene, controls the proteolytic processing of amyloid-beta precursor protein and the formation of the amyloid plaques (Pereira Vatanabe et al, 2021). In addition, miR-1306-5p expression was significantly downregulated in the oxygen-glucose deprivation/reoxygenation-induced SH-SY5Y cell model, and the upregulation of miR-1306-5p could decrease cerebral ischemia/reperfusion injury (Chen et al, 2019), suggesting miR-1306-5p involves in the cell survival rate and inhibits the cell injury.…”

The role of ADAM10 in astrocytes: Implications for Alzheimer’s disease

“…Platelet ADAM10 activity also correlates with measures of cognitive function, suggesting lower ADAM10 is related to worse cognitive function in people with AD ( Manzine et al, 2013 , 2014 ). However, when measuring ADAM10 protein levels in plasma and cerebral spinal fluid, an apparent opposite relationship has been shown, where elevated ADAM10 has been reported in people with AD ( Pereira Vatanabe et al, 2021 ). As ADAM10 is active as a membrane protease it is likely that soluble ADAM10 has undergone ectodomain shedding by other members of the ADAM family, and thus represents a soluble inactive protein ( Parkin and Harris, 2009 ; Pereira Vatanabe et al, 2021 ).…”

“…However, when measuring ADAM10 protein levels in plasma and cerebral spinal fluid, an apparent opposite relationship has been shown, where elevated ADAM10 has been reported in people with AD ( Pereira Vatanabe et al, 2021 ). As ADAM10 is active as a membrane protease it is likely that soluble ADAM10 has undergone ectodomain shedding by other members of the ADAM family, and thus represents a soluble inactive protein ( Parkin and Harris, 2009 ; Pereira Vatanabe et al, 2021 ). Therefore, elevated soluble levels of ADAM10 may be linked to reduced overall enzyme activity.…”