Alzheimer's disease (AD), the most common form of dementia in elderly individuals, is characterized by neurofibrillary tangles, extracellular amyloid-β (Aβ) 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, β-Galactosidase, α-Mannosidase, and β-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 Aβ(1-42) degradation. These results could contribute to clarify the molecular mechanisms that affect the imbalanced Aβ production/clearance involved in the pathogenesis of AD.
Keywords: Cathepsin B; Lysosomal enzymes; Monocytes; Sporadic Alzheimer's disease; TFEB; miR-128.
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