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The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The(More)
OBJECTIVE Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. METHODS Amyloid-beta 1 to 42 peptide (A beta(1-42)), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline(More)
Amyloid beta (Abeta) may play a central role in the pathogenesis of Alzheimer disease. A functional gamma-secretase inhibitor, LY450139, was developed that inhibits Abeta formation in whole cell assays, transgenic mice, and beagle dogs. The authors wished to determine the safety and tolerability of this drug, and the reduction of Abeta in plasma and(More)
OBJECTIVES To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti-β-amyloid (Aβ) antibody, in patients with mild-to-moderate Alzheimer's disease. Cognitive measures were also obtained. METHODS In this phase 2, randomized, double-blind, placebo-controlled clinical trial, 52 patients with(More)
OBJECTIVES Active and passive immunization strategies have been suggested as possible options for the treatment of Alzheimer disease (AD). LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD. METHODS Patients with mild to moderate AD were screened and selected for inclusion. Initial(More)
The goal of this study was to identify the optimal combination of magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) biomarkers to predict conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) dementia within two years, for enriching clinical trial(More)
The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET(More)
Huntington's disease (HD) is a progressive neurodegenerative disorder recently shown to be due to an excess number of CAG trinucleotide repeats in the 5' translated region of chromosome 4. One of the cardinal features of HD is cognitive decline. While mental deterioration is obvious later in the disease course, the time of its onset is difficult to(More)
OBJECTIVE To determine whether changes in motor function and reaction time are present in presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN A case-control, double-blind study comparing asymptomatic at-risk subjects, with or without the HD allele, and subjects clinically determined to have early manifest HD. SETTING The(More)
The close correlation between abnormally low pre-mortem cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ(1-42)) and plaque burden measured by amyloid imaging as well as between pathologically increased levels of CSF tau and the extent of neurodegeneration measured by MRI has led to growing interest in using these biomarkers to predict the(More)