Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

Abstract

Substantial basic science and clinical evidence suggests that excess tumor necrosis factor-alpha (TNF-alpha) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks. TNF-alpha has also recently been shown to mediate the disruption in synaptic memory mechanisms, which is caused by beta-amyloid and beta-amyloid oligomers. The efficacy of etanercept, a biologic antagonist of TNF-alpha, delivered by perispinal administration, for treatment of Alzheimer's disease over a period of six months has been previously reported in a pilot study. This report details rapid cognitive improvement, beginning within minutes, using this same anti-TNF treatment modality, in a patient with late-onset Alzheimer's disease. Rapid cognitive improvement following perispinal etanercept may be related to amelioration of the effects of excess TNF-alpha on synaptic mechanisms in Alzheimer's disease and provides a promising area for additional investigation and therapeutic intervention.

Figure 1

Rapid and sustained improvement in Visuospatial/Executive function following perispinal etanercept documented by the Montreal Cognitive Assessment. The top panel depicts the first three tasks from the Montreal Cognitive Assessment completed by the patient one day prior to perispinal etanercept administration. The middle panel depicts the patient's results two hours after perispinal etanercept administration, showing correct completion of the alternating trail making task documenting improved executive function, and improvement in depiction of a clock face. The bottom panel depicts the patient's results at seven weeks, fourteen days after receiving his previous dose of perispinal etanercept, showing further improvement in his drawing of the clock face, with numerals added, and persistence in improvement in completion of the trail making task. (The instruction for completion of the alternating trail making task are as follows: Please draw a line, going from a number to a letter in ascending order. Begin here [point to (1)] and draw a line from 1 then to A then to 2 and so on. End here [point to (E)]).