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Appreciation of the role that inflammatory mediators play in Alzheimer's disease (AD) pathogenesis continues to be hampered by two related misconceptions. The first is that to be pathogenically significant a neurodegenerative mechanism must be primary. The second is that inflammation merely occurs to clear the detritis of already existent pathology. The(More)
In the course of analyzing the chemical composition of Alzheimer's disease neuritic and vascular amyloid, we have purified stable dimeric and trimeric components of Abeta peptides. These peptides (molecular mass 9.0 and 13.5 kDa) were separated by size exclusion chromatography in the presence of 80% formic acid or 5 guanidine thiocyanate, pH 7.4. The(More)
Traditionally, researchers have used either off-the-shelf models such as COCOMO, or developed local models using statistical techniques such as stepwise regression, to obtain software effort estimates. More recently, attention has turned to a variety of machine learning methods such as artificial neural networks (ANNs), case-based reasoning (CBR) and rule(More)
Brain deposition of the amyloid beta-peptide (Abeta) is a critical step in the pathogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopathy (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of Abeta, but for the majority, there is no known direct genetic cause. We have(More)
Alzheimer disease (AD) is characterized by excessive deposition of the beta-amyloid peptide (beta-AP) in the central nervous system. Although several lines of evidence suggest that beta-AP is neurotoxic, a mechanism for beta-AP toxicity in AD brain remains unclear. In this paper we provide both direct in vitro evidence that beta-AP can bind and activate the(More)
The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. We have characterized C5b-9 and its C9(More)
Recent studies showing that microglia internalize the amyloid beta-peptide (Abeta) suggest that these cells have the potential for clearing Abeta deposits in Alzheimer's disease, and mechanisms that regulate the removal of Abeta may therefore be of clinical interest. Previous studies from this laboratory showing that C1q enhances phagocytosis of cellular(More)
Microglial activation has been associated with several degenerative diseases of the central nervous system (CNS). One consequence of activation is the induction of a more efficient phagocytic response, and it is therefore important to determine what factors regulate microglial phagocytosis and whether this capacity influences the progression of(More)
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(More)
In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on(More)