Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-beta (A beta) plaques and neuroinflammation. New evidence has shown that the lysosomal system might be a crossroad in which etiological factors in AD pathogenesis converge. This study shows that several lysosomal enzymes, including Cathepsin B, D, S, beta-Galactosidase, alpha-Mannosidase, and beta-Hexosaminidase, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared with cells from healthy controls. In vitro experiments of gain and loss of function suggest that down-regulation is a direct consequence of miR-128 up-regulation found in AD-related cells. The present study also demonstrates that miR-128 inhibition in monocytes from AD patients improves A beta(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced A beta production/clearance involved in the pathogenesis of AD. (C) 2014 Elsevier Inc. All rights reserved.
miR128 up-regulation correlates with impaired amyloid beta(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease
Orlacchio Antonio
2014
Abstract
Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-beta (A beta) plaques and neuroinflammation. New evidence has shown that the lysosomal system might be a crossroad in which etiological factors in AD pathogenesis converge. This study shows that several lysosomal enzymes, including Cathepsin B, D, S, beta-Galactosidase, alpha-Mannosidase, and beta-Hexosaminidase, were less expressed in monocytes and lymphocytes from patients with a clinical diagnosis of AD dementia compared with cells from healthy controls. In vitro experiments of gain and loss of function suggest that down-regulation is a direct consequence of miR-128 up-regulation found in AD-related cells. The present study also demonstrates that miR-128 inhibition in monocytes from AD patients improves A beta(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced A beta production/clearance involved in the pathogenesis of AD. (C) 2014 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.