Bennett DA, McDermott MP.
Cerebrospinal fluid shunting for Alzheimer's disease?.
Neurology. 2002 Oct 22;59(8):1126-7.
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Alzheimer’s disease (AD) brain is characterized by progressive and diffuse accumulation of neuritic plaques and neurofibrillary tangles, which are composed of deposits of amyloid-β peptide (Aβ) and abnormally phosphorylated tau protein. In the recent past, a considerable effort has been made to develop methods to retard their deposition or improve their clearance. As a result, Aβ has become a realistic target for developing effective therapies for AD. However, after some promising and exciting data from animal studies with vaccines against Aβ, preliminary negative results in AD patients have tempered the initial enthusiasm.
In this study, Silverberg et al. treated AD patients for 12 months with a low-flow CSF drainage and found reductions in CSF Aβ (1-42) and tau, which were associated with a stabilization of their cognitive function. These results would be consistent with the hypothesis that improving CSF circulation may result in slowing the progression of AD.
There are several aspects of this pilot study that need to be taken into account: 1) the sample size was too small to provide a definitive test of the hypothesis; 2) the study was not double-blind; 3) the controls did not receive any surgery, so a placebo effect cannot be ruled out. Despite these considerations, I believe that this study is very exciting and interesting. The results justify a compelling rationale for a randomized, larger and controlled clinical trial, which could give us clear and definitive answers. Considering that today the main pharmacological interventions for AD offer only minor and transient symptomatic benefit, CSF shunting could be considered as a completely novel and promising approach to treat AD.