July 2, 2018

expert reaction to low-dose aspirin and amyloid plaques

A new study, published in JNeurosci, investigates if a low-dose aspirin regimen may represent a new avenue for reducing Alzheimer’s disease pathology.

Prof Peter Passmore, Professor of Ageing and Geriatric Medicine, Queen’s University Belfast, said:

“This is an interesting study. There have been suggestions that aspirin may be beneficial in Alzheimer’s disease so it is interesting to see these results in an animal model. The study design and the experiments seem fine and the effect on amyloid, which is thought to be one of the key features in Alzheimer’s is of interest. As the authors say this finding needs a lot more research as the results are not conclusive. It will take quite a bit of further research before studies would be done in the appropriate patient group. It has been shown in patients with Alzheimer’s that use of aspirin is associated with an increased risk of intracerebral haemorrhage (Lancet Neurology 2008 Jan;7(1):41-9) so it is important that patients do not start to self-medicate with aspirin in the hope of preventing or mitigating Alzheimer’s.”

Prof Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said:

“This very comprehensive work involves work treating nerve cells and also work with Alzheimer mice.  The main value of the findings are in showing some novel mechanisms related to different Alzheimer pathways which are influenced by aspirin and which may impact on the accumulation of the protein amyloid in the brain.  The paper also includes a small study directly showing a substantial reduction in amyloid In Alzheimer mice.

“Whilst this work is interesting, a lot of previous work has focussed on aspirin or similar drugs as potential approaches to treat or prevent Alzheimer’s disease, with contradictory epidemiological studies and some disappointing clinical trials.   A number of compounds have achieved this level of amyloid reduction in mice, yet have subsequently failed in clinical trials in humans. The failures may be as a result of the differences between Alzheimer mice and human pathology, and the poor translation of benefits into humans.

“Given that there are existing clinical studies, it feels unlikely that aspirin will be a new clinical breakthrough in the treatment of people with Alzheimer’s disease. Aspirin is associated with a risk of gastro-intestinal problems such as ulcers, which must also be balanced against any benefits.”

Dr Sara Imarisio, Head of Research of Alzheimer’s Research UK, said:

“Aspirin is a commonly taken medicine for a number of health conditions, but there has been little research to examine potential benefits for Alzheimer’s disease. This early-stage research suggests aspirin may help improve how the brain removes amyloid, a protein known to build up in Alzheimer’s. The study reveals important insights into the mechanisms through which aspirin may impact brain health, however this is a small study in mice so it’s too early to draw conclusions about whether aspirin could be used to treat Alzheimer’s in people.

“Ultimately the only way to see whether aspirin could help treat Alzheimer’s disease is through large-scale, well-controlled clinical trials in people. Alzheimer’s Research UK is currently funding a study at the University of Oxford examining the effect of aspirin on memory and thinking in people at higher risk of dementia. In this study, aspirin is being investigated for its potential to reduce the risk of developing dementia, which could have a significant impact on healthy ageing.”

Prof Rob Howard, Professor of Old Age Psychiatry, UCL, said:

“This is a well conducted study, showing that, in a mouse model of one of the pathological features of Alzheimer’s disease, aspirin treatment can reduce the amount of this pathology in the brain. Before anyone gets too excited about the implications for treatments in people, I would remind readers of two points. First, mice don’t get Alzheimer’s disease and we have learned the bitter lesson from many studies in the field that what “works” in the mouse models of the disease has not yet worked in our patients. Second, clinical trials of aspirin have already been performed in patients with Alzheimer’s disease. The drug had no beneficial effects on outcome measures and was associated with an increased risk of gastrointestinal haemorrhage.”

Prof Tara Spires-Jones, Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh and UK Dementia Research Institute Programme Lead, said:

“This paper by Prof Pahan and colleagues at Rush University shows that in cells and a mouse model of Alzheimer’s disease, aspirin boosts the ability of brain cells to break down amyloid beta, one of the toxic molecules involved in the disease.  While this work is scientifically interesting, it is at very early stages. The amyloid reducing effects of aspirin were shown in cells in a dish and in a single mouse model of Alzheimer’s disease with relatively few mice per group (6 treated with aspirin and 6 treated with a placebo-like control for each experiment).  Further, the study did not show whether aspirin helped the brain function in this disease model.  More work will need to be done in order to know whether low-dose aspirin could help prevent or treat Alzheimer’s.”

* ‘Aspirin induces Lysosomal biogenesis and attenuates Amyloid plaque pathology in a mouse model of Alzheimer’s disease via PPARα’ by Chandra et al. published in JNeurosci on Monday 2^nd July.

Declared interests

Prof Peter Passmore: “I have no conflict of interest on this one”

Prof Rob Howard: “Has received funding from MRC, NIHR and Alzheimer’s Society to conduct clinical trials in Alzheimer’s disease.”

Dr Sara Imarisio: None

Prof Tara Spires-Jones: “I have no conflicts with this work.”