BrainBlog

From Pharmalot blog, a good read about the Amyvid approval decision: Should FDA Have Approved Lilly Alzheimer’s Agent? Pharmalot By Ed Silverman April 9th, 2012 // 11:23 am Read the full blog post

Intraneuronally Injected Amyloid Beta Inhibits Long-Term Potentiation In Rat Hippocampal Slices J Neurophysiol. 2012 Feb 15; Nomura I, Takechi H, Kato N Abstract Extracellular accumulation of amyloid beta (Aβ) is a hallmark of Alzheimer's disease (AD). It has been reported that extracellular perfusion of Aβ inhibits long-term potentiation (LTP), which is strongly related to memory in animal models. However, it has recently been proposed that intracellular Aβ may be the first pathological change to occur in AD. Here, we have investigated the effect on LTP of intracellular injection of Aβ (Aβ(1-40), Aβ(1-42)) into hippocampal pyramidal cells using patch clamp technique. We found that injection of 1 nM Aβ(1-42) completely blocked LTP and extracellular perfusion of a p38 MAPK inhibitor or a metabotropic glutamate receptor blocker reversed these blocking effects on LTP. Furthermore, we have examined the effects of different concentrations of Aβ(1-40) and Aβ(1-42) on LTP and showed that...

Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation Neuron . 2011 Sep 8; 71(5): 833-844. Kummer MP, Hermes M, Delekarte A, Hammerschmidt T, Kumar S, Terwel D, Walter J, Pape HC, König S, Roeber S, Jessen F, Klockgether T, Korte M, Heneka MT Abstract Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inh...

An NIH Public Access Author Manuscript: Richard J. O’Brien and Philip C. Wong Amyloid Precursor Protein Processing and Alzheimer’s Disease Published in final edited form as: Annu Rev Neurosci. 2011 ; 34: 185–204. doi:10.1146/annurev-neuro-061010-113613. Download the free-access pdf here This looks like a fine overview of our current knowledge.

J&J Will Seek FDA Approval by 2013 for Alzheimer’s Drug Bloomberg News By Alex Nussbaum May 26, 2011 10:38 AM CT Read the news article

A fuller report from The New York Times : F.D.A. Sees Promise in Alzheimer’s Imaging Drug By GINA KOLATA The New York Times Published: January 20, 2011 "A committee voted that the agency should approve the first test that can show the characteristic plaques of Alzheimer’s disease in the brain of a living person." Read the full article

From The New York Times : F.D.A. Sees Promise in Alzheimer’s Imaging Drug By THE ASSOCIATED PRESS Published: January 20, 2011 Filed at 5:40 p.m. EST WASHINGTON (AP) — A federal panel of medical experts said Thursday a first-of-a-kind imaging chemical designed to help screen for Alzheimer's disease could be useful pending additional study and training for physicians. The Food and Drug Administration panel of advisers voted 16-0 in favor of approval for Eli Lilly's Amyvid on the condition that the company demonstrates the images can be consistently interpreted by physicians who have received training in reading the scans. Without those requirements the panel voted 13-3 against approval for the injection in an earlier vote. The FDA is not required to follow the panel's advice, though it often does. Read the full report

From The New York Times : Tests Show Promise for Early Diagnosis of Alzheimer’s By GINA KOLATA The New York Times Published: January 18, 2011 "Researchers report major advances on two vexing questions about Alzheimer’s: How do you know if someone who is demented has it? And how can you screen the general population for risk?" Read the full article. The report includes discussion about this week's forthcoming FDA Advisory Committee discussion about Avid Radiopharmaceuticals product.

From the NIH: Impaired clearance, not overproduction of toxic proteins, may underlie Alzheimer’s disease 09 December 2010 In Alzheimer's disease, a protein fragment called beta-amyloid accumulates at abnormally high levels in the brain. Now researchers funded by the National Institutes of Health have found that in the most common, late-onset form of Alzheimer’s disease, beta-amyloid is produced in the brain at a normal rate but is not cleared, or removed from the brain, efficiently. In addition to improving the understanding of what pathways are most important in development of Alzheimer's pathology, these findings may one day lead to improved biomarker measures for early diagnosis as well as a new approach to treating this devastating disorder. Many believe that accumulation of abnormal levels of beta-amyloid in the brain initiates a cascade of events leading to the death of brain cells and ultimately to dementia. In the rare, early-onset forms of Alzheimer's that are link...

Old Enemy Might Help to Prevent Alzheimer’s By GINA KOLATA The New York Times Published: March 8, 2010 "Harvard researchers are taking a new look at beta amyloid, which was thought to be a chief villain in Alzheimer’s whose function was that of a waste product in the brain." Read the full article

A Bloomberg News report about the state of clinical trials of those Alzheimer's disease candidates in the processes/stages in amyloid levels and amyloid deposition: read article here