Reduction of Alzheimer’s Disease Amyloid Plaque Load in Transgenic Mice by D3, a D-Enantiomeric Peptide Identified by Mirror Image Phage Display

ChemMedChem ◽  
2008 ◽  
Vol 3 (12) ◽  
pp. 1848-1852 ◽  
Author(s):  
Thomas van Groen ◽  
Katja Wiesehan ◽  
Susanne A. Funke ◽  
Inga Kadish ◽  
Luitgard Nagel-Steger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Phage Display ◽  
Amyloid Plaque ◽  
Mirror Image ◽  
Plaque Load

scholarly journals Bacterial sepsis increases hippocampal fibrillar amyloid plaque load and neuroinflammation in a mouse model of Alzheimer's disease

2021 ◽  
Vol 152 ◽  
pp. 105292
Author(s):  
Jacob M. Basak ◽  
Aura Ferreiro ◽  
Lucy S. Cohen ◽  
Patrick W. Sheehan ◽  
Collin J. Nadarajah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Plaque ◽  
Bacterial Sepsis ◽  
Model Of Alzheimer’S Disease ◽  
Plaque Load

Donanemab (LY3002813) Phase 1b Study in Alzheimer’s Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir F18 Imaging

2021 ◽  
pp. 1-11
Author(s):  
S.L Lowe ◽  
C. Duggan Evans ◽  
S. Shcherbinin ◽  
Y.-J. Cheng ◽  
B.A. Willis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Single Dose ◽  
Standard Error ◽  
Amyloid Plaque ◽  
Emission Tomography ◽  
Positron Emission ◽  
Plaque Load ◽  
Antidrug Antibodies

Background: Donanemab (LY3002813) is an IgG1 antibody directed at an N‑terminal pyroglutamate of amyloid beta epitope that is present only in brain amyloid plaques. Objectives: To assess effects of donanemab on brain amyloid plaque load after single and multiple intravenous doses, as well as pharmacokinetics, safety/tolerability, and immunogenicity. Design: Phase 1b, investigator- and patient-blind, randomized, placebo-controlled study. Setting: Patients recruited at clinical research sites in the United States and Japan. Participants: 61 amyloid plaque-positive patients with mild cognitive impairment due to Alzheimer’s disease and mild-to-moderate Alzheimer’s disease dementia. Intervention: Six cohorts were dosed with donanemab: single dose 10-, 20- or 40- mg/kg (N = 18), multiple doses of 10-mg/kg every 2 weeks for 24 weeks (N = 10), and 10- or 20-mg/kg every 4 weeks for 72 weeks (N=18) or placebo (N = 15). Measurements: Brain amyloid plaque load, using florbetapir positron emission tomography, was assessed up to 72 weeks. Safety was evaluated by occurrence of adverse events, magnetic resonance imaging, electrocardiogram, vital signs, laboratory testing, neurological monitoring, and immunogenicity. Results: Treatment with donanemab resulted in rapid reduction of amyloid, even after a single dose. By 24 weeks, amyloid positron emission tomography mean changes from baseline for single donanemab doses in Centiloids were: -16.5 (standard error 11.22) 10-mg/kg intravenous; 40.0 (standard error 11.23) 20 mg/kg intravenous; and -49.6 (standard error 15.10) 40-mg/kg intravenous. Mean reduction of amyloid plaque in multiple dose cohorts by 24 weeks in Centiloids were: 55.8 (standard error 9.51) 10-mg/kg every 2 weeks; -50.2 (standard error 10.54) 10-mg/kg every 4 weeks; and -58.4 (standard error 9.66) 20-mg/kg every 4 weeks. Amyloid on average remained below baseline levels up to 72 weeks after a single dose of donanemab. Repeated dosing resulted in continued florbetapir positron emission tomography reductions over time compared to single dosing with 6 out of 28 patients attaining complete amyloid clearance within 24 weeks. Within these, 5 out of 10 patients in the 20 mg/kg every 4 weeks cohort attained complete amyloid clearance within 36 weeks. When dosing with donanemab was stopped after 24 weeks of repeat dosing in the 10 mg every 2 weeks cohort, florbetapir positron emission tomography reductions were sustained up to 72 weeks. For the single dose cohorts on day 1, dose proportional increases in donanemab pharmacokinetics were observed from 10 to 40 mg/kg. Dose proportional increases in pharmacokinetics were also observed at steady state with the multiple dose cohorts. Donanemab clearance was comparable across the dose levels. Mean donanemab elimination-half-life following 20 mg/kg single dose was 9.3 days with range of 5.6 to 16.2 days. Greater than 90% of patients had positive treatment-emergent antidrug antibodies with donanemab. However, overall, the treatment-emergent antidrug antibodies did not have a significant impact on pharmacokinetics. Donanemab was generally well tolerated. Amongst the 46 participants treated with donanemab, the following amyloid-related imaging abnormalities, common to the drug class, were observed: 12 vasogenic cerebral edema events (12 [19.7%] patients), 10 cerebral microhemorrhage events (6 [13.0%] patients), and 2 superficial siderosis events (2 [4.3%] patients). Conclusions: Single and multiple doses of donanemab demonstrated a rapid, robust, and sustained reduction up to 72 weeks in brain amyloid plaque despite treatment-emergent antidrug antibodies detected in most patients. Amyloid-related imaging abnormalities were the most common treatment-emergent event.

scholarly journals Hippocampal Neuron Loss Exceeds Amyloid Plaque Load in a Transgenic Mouse Model of Alzheimer's Disease

2004 ◽  
Vol 164 (4) ◽  
pp. 1495-1502 ◽  
Author(s):  
Christoph Schmitz ◽  
Bart P.F. Rutten ◽  
Andrea Pielen ◽  
Stephanie Schäfer ◽  
Oliver Wirths ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Hippocampal Neuron ◽  
Amyloid Plaque ◽  
Transgenic Mouse Model ◽  
Neuron Loss ◽  
Model Of Alzheimer’S Disease ◽  
Plaque Load

IC-P-113: [18 F]BAY 94-9172 PET: Towards in vivo quantification of brain β-amyloid plaque load in Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_2) ◽  
pp. P47-P47
Author(s):  
Osama Sabri ◽  
Henryk Barthel ◽  
Georg Becker ◽  
Julia Luthardt ◽  
Marianne Patt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaque ◽  
Plaque Load ◽  
Β Amyloid

scholarly journals Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease

2014 ◽  
Vol 35 (8) ◽  
pp. 1792-1800 ◽  
Author(s):  
Michael B. Dinkins ◽  
Somsankar Dasgupta ◽  
Guanghu Wang ◽  
Gu Zhu ◽  
Erhard Bieberich
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Plaque ◽  
Model Of Alzheimer’S Disease ◽  
Plaque Load ◽  
5Xfad Mouse

P1-285: First results toward in vivo quantification of cerebral β-amyloid plaque load in Alzheimer's disease by means of BAY 94-9172-PET

2008 ◽  
Vol 4 ◽  
pp. T301-T301
Author(s):  
Osama Sabri ◽  
Henryk Barthel ◽  
Marianne Patt ◽  
Eva Hammerstein ◽  
Georg Becker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaque ◽  
Plaque Load ◽  
First Results ◽  
Β Amyloid
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