It has recently been reported that a drug currently used to treat rheumatoid arthritis (RA) may also pack a punch in the fight against Alzheimer’s disease (AD). This discovery may be hailed by the media as a big step forward for AD research but what does it really mean?
To pick apart this discovery, we first need to delve into some background on Alzheimer’s itself:
Much of what we know about Alzheimer’s disease in the human brain comes from postmortem studies. This means that most of our knowledge is skewed towards late stages of the disease. We know that, in these late stages, patient’s brains are severely shrunken and littered with clusters of abnormal proteins known as amyloid plaques and tau tangles. Many academics acknowledge that if we want to successfully treat AD it’s important that we understand what causes these proteins to misbehave in the first place. This is where scientists picked up on an important link between RA and AD.
Rheumatoid arthritis is an autoimmune disease which causes inflammation, pain and swelling in joints. Interestingly, alongside chronic inflammation, many RA sufferers also experience what is known as secondary amyloidosis resulting from deposition of amyloid protein fibrils. This form of amyloid starts life in the liver before being cut into smaller pieces and then deposited in other tissues – importantly this process appears to parallel the deposition of amyloid in the AD brain. Another important parallel between the two diseases is the presence of tumor necrosis factor (TNF) – a pro-inflammatory cytokine. Researchers believe that RA may be driven by TNF and it is also known that AD patients show elevated levels of TNF in their cerebrospinal fluid.
So, is it possible that TNF could play a causative role in both RA and AD and, if so, can modulation of TNF be used as a treatment for both diseases?
In a recent study Richard C.Chou from Dartmouth-Hitchcock Medical Centre collected medical records from over 8,000,000 US patients and his team began crunching numbers in the hope of answering these questions. They found that patients suffering from RA (over 40,000 patients) had a significantly increased risk of also developing AD. In fact, RA patients over the age of 65 were more than twice as likely to suffer from AD than non-sufferers (2.95% of RA patients also suffered from AD in comparison to 1.37% of non-RA patients). What was even more interesting was that patients treated with the RA drug etanercept (an anti-TNF agent) were significantly less likely to suffer from AD than other RA patients.
These results suggest that both RA and AD may share a common mechanism, perhaps linked by the actions of TNF? It also raises the possibility that anti-TNF therapies could have a future in the treatment of AD.
Although this work is just one more piece in the Alzheimer’s puzzle, the implications seem to suggest a role for inflammation and perhaps TNF in disease progression – something which has also been highlighted in previous studies. So, although (as is often the case) more research is needed, it does seem like we are making some significant headway in understudying and hopefully treating Alzheimer’s.
Post by: Sarah Fox