Aspirin is one of the most commonly used drugs in the world and a number of past studies have suggested that it may be protective against neurodegenerative diseases, such as Alzheimer’s disease.

The study by Chandra and colleagues is exciting because it investigates a novel brain mechanism by which aspirin might assert these effects.

Through a series of elegant experiments, they demonstrate that aspirin is able to enhance the activity of lysosomes, which act as a rubbish disposal for the cell. By augmenting the activity of these lysosomes using aspirin, Chandra and colleagues were able to show an enhanced uptake and breakdown of amyloid beta, one of the key pathological brain markers of Alzheimer’s disease.

In Alzheimer’s disease, amyloid beta forms toxic aggregates known as senile plaques outside of brain cells; however, with aspirin treatment, the uptake and breakdown of amyloid beta by lysosomes was enhanced and amyloid pathology and plaque burden was reduced both in cell culture and in an experimental model of Alzheimer’s disease.

While this could lead to exciting new treatment targets for Alzheimer’s, a number of cautions need to be taken in interpreting the study results.

Firstly, to date, the majority of clinical studies that have attempted to target amyloid beta for the treatment of Alzheimer’s disease have failed to generate clinically relevant improvements in cognitive function.

Given that Chandra and colleagues did not include any measures of cognitive function in their experimental model, this concern is particularly relevant.

Additionally, while it is true that observational studies have suggested that anti-inflammatory drugs, such as aspirin, may help to reduce the risk of Alzheimer’s disease, randomized clinical trials have failed to support these benefits. Thus, while potentially exciting, a significant amount of additional experimental evidence is required.

This paper reports that low-dose aspirin protects against an animal model of Alzheimer’s disease. While plausible and encouraging, don’t rush out to start taking low-dose Aspirin yet.

One of the key hallmarks of Alzheimer’s disease is the accumulation in the brain of a toxic, insoluble protein aggregate. While there is a lot of evidence that this toxic protein plays a role in Alzheimer’s disease, why it starts accumulating, and whether there is a deeper pathology that this toxic aggregate is an indicator of, are still widely debated.

What is becoming increasingly recognised is that a defect in the body’s “garbage collection” mechanisms play a role in the accumulation of the toxic protein. Low-dose aspirin is widely used to reduce the risk of heart attack and stroke. It does this in a number of ways, by reducing the ability of the blood to clot as reducing inflammation.

However, aspirin also appears to stimulate the body’s “garbage collection” mechanisms, increasing removal of the toxic protein aggregate, and protecting mice that have Alzheimer’s disease-like pathology from increased levels of the toxic protein aggregate.

However, we have several drugs which were very effective in these models, all of which have failed in human clinical trials.

This may be because our understanding of Alzheimer’s disease is fundamentally flawed, or that we must start giving these drugs many years before the disease manifests. There is a lot of epidemiological evidence that long-term consumption of anti-inflammatory drugs related to aspirin is associated with a lower risk of Alzheimer’s Disease, but clinical trials where the drugs are given in a controlled manner have been inconclusive.

We will need to do a lot more work to determine if consuming low-dose aspirin will be effective at reducing Alzheimer’s disease risk.

This is very interesting study supports the notion that aspirin may help reduce Alzheimer’s disease.

The study comes from Kalipada Pahan's team (Rush University Medical Center, Chicago, IL). The cause of Alzheimer’s has been thought to be due to accumulation of amyloid. However this remains unproven.

Current therapies directed to remove plaque from the brain have so far failed. Therefore there is great interest in alternative approaches to solving this disease.

Previous studies of large populations of people (called epidemiological studies) have shown that taking aspirin may reduce the risks of Alzheimer’s disease. This new paper supports the idea that aspirin may in fact assist in treating Alzheimer’s, though there would be a lot more work to do.

The intriguing aspect of this study is to suggest that aspirin may do this in a very novel way, namely by activating the cellular machinery responsible for removing waste from the brain; this presumably in addition to its anti-inflammatory actions that we believe would be important in Alzheimer’s disease.

The findings are very interesting and offer an interesting basis for further work on new approaches to solving Alzheimer’s. 

An important thing to note is that long-term aspirin use has several side effects including thinning the blood and causing stomach ulcers. Therefore people should take care before taking aspirin long-term and should consult their doctor.