Mammals such as us humans can lose their memory and other mental abilities by a variety of causes, leading to a condition called dementia. About 2/3 to 3/4 of all dementias are caused by a subtype called Alzheimer’s dementia, or AD. Other dementias are caused by accumulating lots of little infarcts in the brain, called vascular dementia, and there are still other causes which are less frequent.
AD is caused by the formation of tangles of abnormal Tau protein inside nerve cells, and plaques of a peptide called beta-amyloid in between the nerve cells and fibres in the brain. Here is a schematic of what happens :
In those unaffected by AD, the beta-amyloid gets constantly cleaned up and plaques do not form, a process facilitated by another protein called Apolipoprotein E (ApoE), that is coded for on chromosome 19.
Risk factors for AD include genetic susceptibility (AD can run in families), advanced age, lower intelligence, small head size, and history of head trauma.
There is a study out in the Journal Science this week that reports success in reducing plaque load with subsequent improval of cognitive function in a mouse model of AD, by stimulating ApoE expression through the administration of a cancer drug called Bexarotene :
Oral administration of the RXR agonist, bexarotene, to a murine model of Alzheimer’s disease resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced >50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the very rapid reversal of a broad range of Aβ-induced deficits.
I always have a bit of a bad feeling when I report on these things. Because I know how many people and their loved ones are affected by this disease, and how desperately the world needs a treatment option for AD, given the fact that it already affects around 20% of those over the age of 80 and is going to cause severe challenges for health systems and aged care facilities all over the world.
But this is preliminary research on an animal model, mice are not men (and mouse brains are not human brains), and drugs that work in mice may not work in humans. So we all have to be patient and await human trials of this and other drugs that are currently being considered for the treatment of AD. But this, if the results can be reproduced in humans, is great news, and looks indeed promising.
Yes Martin, I saw a reference to this in ‘Science Daily’ and I’m pretty sure that anyone here will recognise it for what it is, a promising line for further research. You can bet your sweet life that morons writing in the press will have a field day with headlines trumpeting ‘Men In White Coats Cure Alzheimer’s!’ or similar.
Obviously human trials will be years away, but given that our pet mice are becoming increasingly forgetful, frankly I’m excited!