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Apolipoprotein E (apoE), a plasma apolipoprotein that plays a central role in lipoprotein metabolism, is localized in the senile plaques, congophilic angiopathy, and neurofibrillary tangles of Alzheimer disease. Late-onset familial and sporadic Alzheimer disease patients have an increased frequency of one of the three common apoE alleles, epsilon 4,(More)
Amyloid beta-peptide (A beta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in A beta deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a(More)
Pathological degeneration of neurons in Huntington's disease and associated neurodegenerative disorders is directly correlated with the expansion of CAG repeats encoding polyglutamines of extended length. The physical properties of extended polyglutamines and the intracellular consequences of expression of polyglutamine expansion have been the object of(More)
The frequency of the allele for apolipoprotein E type 4 (epsilon 4) is increased in late-onset familial and sporadic Alzheimer's disease (AD). We have examined epsilon 4 frequencies in four distinct, normal, elderly control groups and, most importantly, in patients with amyloid-forming diseases whose epsilon 4 distributions were not previously known(More)
Neurodegenerative disorders of aging are characterized by the intraneuronal accumulation of ubiquitin conjugates into tangles and inclusions. Ubiquitin conjugates are degraded by cellular particles known as proteasomes. We have previously shown that amyloid beta protein (Abeta) inhibits proteasomal activity and thereby blocks ubiquitin conjugate(More)
Ubiquitin-B+1 (UBB+1) is a mutant ubiquitin that accumulates in the neurones of patients with Alzheimer's disease (AD). Here we report on the biochemical and functional differences between ubiquitin and UBB+1 and the effect of the mutant protein on neuronal cells. UBB+1 lacks the capacity to ubiquitinate, and although it is ubiquitinated itself, UBB+1 is(More)
Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the beta peptide of brain amyloid from Alzheimer's disease. The open reading frame of the sequenced clone coded for 97 amino acids, including the known amino acid sequence of this polypeptide. The(More)
BACKGROUND Inflammation has been implicated as a pathogenetic factor in Alzheimer disease, possibly via effects on beta-amyloid (Abeta). Hyperinsulinemia induces inflammation and is a risk factor for Alzheimer disease. Thus, insulin abnormalities may contribute to Alzheimer disease pathophysiology through effects on the inflammatory network. OBJECTIVES To(More)
The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure(More)
We have mapped the neuroanatomical distribution of amyloid-beta-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-beta-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In(More)