title: Complement activation by neurofibrillary tangles in Alzheimer's disease.
abstract: Brain inflammation is widely documented to occur in Alzheimer's disease (AD), but its sources are still incompletely understood. Here, we present in vitro and in situ evidence that, like amyloid beta peptide (Abeta), tau, the major protein constituent of the neurofibrillary tangle, is a potent, antibody-independent activator of the classical complement pathway. Complement activation, in turn, is known to drive numerous inflammatory responses, including scavenger cell activation and cytokine production. Because Abeta deposits and extracellular tangles are present from early preclinical to terminal stages of AD, their ability to activate complement provides a ready mechanism for initiating and sustaining chronic, low-level inflammatory responses that may cumulate over the disease course.
authors.affiliation: Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Lue
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Roher
authors.forename: Y
authors.initials: Y
authors.lastname: Kuo
authors.forename: R
authors.initials: R
authors.lastname: Strohmeyer
authors.forename: W J
authors.initials: WJ
authors.lastname: Goux
authors.forename: V
authors.initials: V
authors.lastname: Lee
authors.forename: G V
authors.initials: GV
authors.lastname: Johnson
authors.forename: S D
authors.initials: SD
authors.lastname: Webster
authors.forename: N R
authors.initials: NR
authors.lastname: Cooper
authors.forename: B
authors.initials: B
authors.lastname: Bradt
authors.forename: J
authors.initials: J
authors.lastname: Rogers
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D015153:Blotting, Western; D003167:Complement Activation; D003171:Complement Pathway, Classical / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D016874:Neurofibrillary Tangles / Q000473:pathology / Q000502:physiology*; D011994:Recombinant Proteins; D016875:tau Proteins / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D016875:tau Proteins