Ultrasound as a Potential Treatment In Alzheimer’s
For years, Alzheimer’s disease had been conflated with ageing; that decline in an individual’s memory and mental acuity must happen to us all. However, though minor change to mental function is indeed inevitable, changes that disrupt daily life are not. This is an important distinction to make, as it underscores that dementia ought not be accepted; rather, developing effective treatments is imperative . Unfortunately, the drive for Alzheimer’s treatment has yet to yield any success; something that we have been reminded of with the recent death of Terry Pratchett, a national treasure diagnosed with the disease in 2007, who recently died due to lack of appropriate treatment.
Alzheimer’s disease is characterised by accumulations of a protein fragment, Aβ, in the brain. This occurs due to increased production of Aβ, and also its reduced clearance, incidentally providing two targets for therapeutic strategies. The first of these involves inhibiting production of Aβ, through targeting a family of protein called the secretases; however, the secretases are involved in the production of proteins besides Aβ, and their inhibition can lead to adverse side-effects. The second strategy involves stimulating Aβ clearance through the patient’s immune system. Though such methods have been demonstrated to reduce Aβ burden and improve cognition, they can cause inflammation in the brain tissue, and are currently expensive. However, a group from the University of Queensland, Australia, have developed a novel method of Aβ clearance in animal models, which is cost-effective, and does not cause inflammation.
The researchers used scanning ultrasound to transiently open the blood-brain barrier in a mouse model of Alzheimer’s disease. This technique utilises inert preformed “microbubbles”. The microbubbles are administered intravenously, and then stimulated at the blood-brain barrier with ultrasound pulses. These pulses cause the microbubbles to expand and contract. Cycles of expansion-contraction exert a mechanical effect upon the vasculature, inducing the opening of channels capable of facilitating transport across the blood-brain barrier. In this study, the transient opening of the blood-brain barrier recruits the brain’s resident immune cells, microglia, to internalise and digest Aβ. This was associated with an improvement of cognitive performance in a range of tests.
There are several barriers yet to be overcome, such as the larger brains and thicker skulls of humans; however, the authors suggest human trials will commence by 2017. The research also has broader implications, as these methods could be used to deliver drugs across the blood-brain barrier. There may also be other elements influencing Aβ clearance here; of particular note is albumin, which is present at high concentrations in the blood, and may sequester Aβ; however, further work would need to be done to determine whether albumin is an important factor in the present study.
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