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The protease inhibitor alpha 1-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposits of Alzheimer's disease. We report here that these two amyloid-associated proteins serve a strong stimulatory role in the polymerization of A beta(More)
Two approaches--molecular cloning and immunochemical analysis--have identified one of the components of Alzheimer's disease amyloid deposits as the serine protease inhibitor alpha 1-antichymotrypsin. An antiserum against isolated Alzheimer amyloid deposits detected immunoreactivity in normal liver. The antiserum was then used to screen a liver cDNA(More)
Currently Alzheimer's disease, which affects more than 20 million people worldwide, can only be definitely diagnosed by histological examination of brain tissue obtained at autopsy or biopsy. There is a great need for an early, noninvasive, sensitive, and easily administered diagnostic test of Alzheimer's disease. Here it is reported that patients diagnosed(More)
The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the(More)
The amyloid deposits of Alzheimer's disease contain, in addition to the beta protein (A beta), lesser amounts of other proteins including the protease inhibitor alpha 1-antichymotrypsin (ACT). We have recently shown that ACT acts as a pathological chaperone, binding to the beta protein and strongly promoting its polymerization into amyloid filaments in(More)
We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin(More)
BACKGROUND Despite convenience, accessibility, and strong correlation to severity of Alzheimer disease (AD) pathology, medial temporal lobe atrophy (MTA) has not been used as a criterion in the diagnosis of prodromal and probable AD. METHODS Using a newly validated visual rating system, mean MTA scores of three bilateral medial temporal lobe structures(More)
Proinflammatory cytokines and acute phase proteins, such as alpha(1)-antichymotrypsin, are over expressed in microglia and astrocytes in brain regions with abundant mature amyloid plaques, suggesting a glial cell-led brain acute phase response in the Alzheimer neuropathology. In this paper, we show that alpha(1)-antichymotrypsin gene expression in human(More)
Alzheimer's disease is among the most common diseases of advanced age affecting almost one out of ten individuals who survive beyond the age of 65 years, and an another 10% for each additional decade of the life-span. The prognosis of the disease is an inexorable decline of mental functions leading to complete dependence on caretakers in the late stages of(More)