Alzheimer’s Disease – are we forgetting something?
My lasting memory of my grandmother is unfortunately very different to the vibrant and kind woman my parents describe. I remember a frail woman restricted to a nursing home, needing my father’s prompting to remember our names whenever my brothers and I would visit her.
I must admit I never liked going when I was young; I found the smell of the nursing home off-putting. However, I think seeing this group of adults, robbed of their faculties so they couldn’t even maintain a conversation, was the most frightening aspect of my visit.
This is the disabling impact of Alzheimer’s disease. It is the most common form of dementia and affects over 413,000 Australians. With our ageing population, by 2025 it is expected this number will jump up to 536,164.
People affected by Alzheimer’s disease experience gradual memory loss, particularly of recent events, have difficulty finding the right words to say, and lose the ability to plan or solve problems. This makes normal activities in life increasingly challenging. They may misplace their keys, forget to pay bills and cannot follow conversations, so they withdraw from their work or social life.
Alzheimer’s disease is relentless; it progressively rips out the traits that define an individual until they are left helplessly bed-ridden to waste away.
What causes people to end up this way? The simple answer is we do not know. Over time, scans show the brain atrophies and gets smaller, but if the person dies and an autopsy is performed, you can use a microscope to visualise two clues in the ravages that Alzheimer’s disease leaves behind.
A protein called beta-amyloid is deposited in plaques outside of neurons, while inside the brain cells, another protein tau can be seen forming what are known as neurofibrillary tangles.
The extent of these findings correlate with the severity of disease, but we don’t know whether it’s the amyloid plaques or the tangles of tau that are most responsible for the damage. This matters: the target of choice must have substantial time and money dedicated to it if we are to to discover possible treatments.
It has been uncertain and even controversial, with the research community at one time labelling the two sides ‘Tauists’ and ‘Baptists’ to reflect those devoted to the tau and beta-amyloid theories respectively.
Historically beta-amyloid has been considered the most important and therefore the most targeted. One popular method is using antibodies to target the protein and allowing our immune system to clear it.
There are two different methods of doing this – stimulating the body to produce its own antibodies, in a similar way to vaccinations, or injecting antibodies into patients’ bloodstream. So far, major clinical trials have either been stopped due to life-threatening complications or failing to show improvement.
Recently the Doctus Project reported on methods being developed to help these antibodies gain better access to the brain, an avenue that may prove important in future treatment advances.
Many have asked why such major trials have failed. It is possible we have got the timing wrong, targeting people in whom irreversible damage may already have occurred.
However, it may be that we are targeting the wrong thing altogether.
One of the most notable research stories to come out of Australia is about peptic ulcers. Ulcers in the stomach were thought to be caused by stress, but if you reduced the gastric acid production with medication you could heal them, although they would frequently recur. Dr Robin Warren and Dr Barry Marshall had an altogether different hypothesis: they believed peptic ulcers were caused by a bacterium called Helicobacter pylori, and by treating with antibiotics you could permanently cure patients.
The story involves Marshall famously drinking a culture of the bacteria, developing ulcers and by taking the right antibiotics he cured himself.
When they reported their findings they were dismissed out of hand as ludicrous, struggling to overcome the prevailing dogma in medicine that stress caused ulcers. It took a decade before antibiotics were used routinely, but eventually they turned the field of peptic ulcers upside down. For their efforts they were awarded the 2005 Nobel Prize in Physiology or Medicine.
Is it possible there could be a similar paradigm shift on the horizon in Alzheimer’s disease research? In 2015 a group in Spain published a paper in Nature that looked at 11 brains of people who had Alzheimer’s disease and compared to the brains of 11 healthy people of a similar age. What they found was fascinating: in the brain of every individual living with Alzheimer’s was evidence of fungus growing inside the brain tissue. No fungal cells were identified in the brains of the healthy controls. This, they say, could help explain the unknown cause of Alzheimer’s disease; the gradually worsening dementia fits with the slow progression of a chronic fungal infection.
They are not the only ones investigating an infectious trigger. An editorial was published last year by groups of researchers and doctors highlighting the possible microbial link to Alzheimer’s disease. They point the finger at Herpes Simplex Virus Type 1 (HSV-1), a common virus that causes cold sores, that can reach the brain and remain there in a latent form. The markers we thought integral to the development of dementia may actually be markers of infection and our body’s defence mechanisms. These groups argue such theories have been neglected and, given the decade of failures of major clinical trials, research should focus more on infectious causes and trialling medications that treat viruses and fungi to prevent Alzheimer’s disease.
So is Alzheimer’s disease caused by infection? It’s an intriguing theory but so far the evidence is inconclusive. It is hard to know whether these infections cause Alzheimer’s disease, or whether the individuals are more prone to developing infections because of their illness. However, we should not forget the lessons of history when dismissing theories out of hand, no matter how unconventional they appear. Perhaps one day we will be preventing Alzheimer’s disease with commonly used anti-fungal medications.
The views and opinions expressed in this article are those of the author and do not necessarily represent those of the Doctus Project.