Eric R. Siemers

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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)
BACKGROUND Alzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain. METHODS In two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION(More)
Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available 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)
OBJECTIVE Accumulation of amyloid-beta (Abeta) by overproduction or underclearance in the central nervous system (CNS) is hypothesized to be a necessary event in the pathogenesis of Alzheimer's disease. However, previously, there has not been a method to determine drug effects on Abeta production or clearance in the human CNS. The objective of this study(More)
BACKGROUND Alzheimer's disease is characterized by the presence of cortical amyloid-beta (Aβ) protein plaques, which result from the sequential action of β-secretase and γ-secretase on amyloid precursor protein. Semagacestat is a small-molecule γ-secretase inhibitor that was developed as a potential treatment for Alzheimer's disease. METHODS We conducted(More)
OBJECTIVE To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease. DESIGN Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial. SETTING Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer(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)