THREE CARDINAL LESSONS FROM ADAPT – 10 YEARS ON

Author(s):  
J.C.S. Breitner ◽  
C.G. Lyketsos

The Alzheimer’s Disease Anti-inflammatory Prevention Trial was a placebo-controlled three-arm pharmaco-prevention trial of the non-steroidal anti-inflammatory drugs naproxen sodium and celecoxib for prevention of incident Alzheimer’s disease (AD) dementia in older (aged 70 and over) adults. Although subjects were at increased risk of symptoms because of a firstdegree family history, they were meant to be cognitively healthy at enrollment. ADAPT encountered several problems that resulted in the termination of its treatments after only two years on average. Interim results were complex but potentially interesting. In the end, however, the results were null. We describe the complications that prevented ADAPT from achieving conclusive results, and suggest that these could have been avoided if the trial design and execution had been better guided by preliminary data. We believe such data should be available before beginning further ambitious phase III trials of this sort, and we suggest a broad method by which such data can be accumulated with reasonable economy.

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Sara Mahdiabadi ◽  
Sara Momtazmanesh ◽  
George Perry ◽  
Nima Rezaei

Abstract Alzheimer’s disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-β plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.


2010 ◽  
Vol 3 (6) ◽  
pp. 1812-1841 ◽  
Author(s):  
Amy H. Moore ◽  
Matthew J. Bigbee ◽  
Grace E. Boynton ◽  
Colin M. Wakeham ◽  
Hilary M. Rosenheim ◽  
...  

2002 ◽  
Vol 21 (2) ◽  
pp. 81-86 ◽  
Author(s):  
C. Wolfson ◽  
A. Perrault ◽  
Y. Moride ◽  
J.M. Esdaile ◽  
L. Abenhaim ◽  
...  

2015 ◽  
Vol 44 (2) ◽  
pp. 385-396 ◽  
Author(s):  
Jun Wang ◽  
Lan Tan ◽  
Hui-Fu Wang ◽  
Chen-Chen Tan ◽  
Xiang-Fei Meng ◽  
...  

2013 ◽  
Vol 9 ◽  
pp. P138-P138 ◽  
Author(s):  
Johannes Streffer ◽  
Kaj Blennow ◽  
Stephen Salloway ◽  
Henrik Zetterberg ◽  
Yi-Zheng Xu ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document