title: Abnormal Expression and Distribution of MMP2 at Initial Stages of Alzheimer's Disease-Related Pathology.
abstract: Previous studies have shown that metalloproteinases (MMPs) participate in the clearance of amyloid-β (Aβ) in Alzheimer's disease (AD); MMP2 and MMP3 cleave soluble Aβ, and both MMP9 and MT1-MMP are able to degrade soluble and fibrillar forms of Aβ. The present study shows increased expression levels of active MMP2 in the entorhinal cortex at early stages of AD-related pathology (Braak and Braak stages I/II-0 and III/IV-A) as revealed by western blotting and gelatin zymography. Confocal microscopy discloses co-localization of MMP2 and phospho-tau in neurofibrillary tangles and dystrophic neurites. MMP2 has the capacity to cleave recombinant tau in vitro in a dose-dependent manner, consistent with a physiological function of MMP2 in normal tau proteolysis. However, MMP2 does not cleave hyperphosphorylated and dephosphorylated tau from enriched paired helical filament fractions. These observations raise the possibility that accumulation of MMP2 in neurofibrillary tangles and concomitant loss of proteolytic capacity on tau protein is a response geared to eliminating production of toxic truncated tau species in AD brains.
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.|Laboratory of Neurobiology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Spain.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Terni
authors.affiliation: Institute of Neuropathology, Bellvitge University Hospital, Hospitalet de Llobregat, Spain.|University of Barcelona, Hospitalet de Llobregat, Spain.|CIBERNED, Institute Carlos III, Ministry of Health, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018728:Entorhinal Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Alzheimer’s disease; MMP2; metalloproteinases; neurofibrillary tangles; tau