What is Alzheimer’s disease?
Alzheimer’s is a debilitating neurological and degenerative (meaning, it gets worse over time) brain disease. There is a misconception around the difference between dementia and Alzheimer’s disease and the 2 terms are often used synonymously.
However: dementia is the umbrella term for a particular group of symptoms, namely a decline in memory function and ‘thinking skills’ that allow people to carry out regular daily life activities. Dementia can have a number of causes. Alzheimer’s disease is the most common one, accounting for 60% to 80% of dementia cases1.
Alzheimer’s disease can begin over 20 years before symptoms become noticeable. Symptoms occur due to the destruction or damage of nerve cells in the brain.
This initially presents as a decline in cognitive function (how well our brain works to understand and remember information), which will then progress into having difficulties carrying out ‘basic bodily functions,’ such as eating and drinking, as more nerve cells are damaged as the disease progresses.
Unfortunately, the reason for this neuronal destruction remains poorly understood. Considering the lengthy period during which the disease silently causes harm, there is a need to further understand how the damage happens in order to diagnose and help patients earlier.
Currently, dementia caused by Alzheimer’s disease is diagnosed by exclusion - meaning, other disease or causes (e.g. mental health issues, stress, medication, health disturbances such as hormone imbalances, etc.) have to be eliminated before it is considered. Misdiagnosis of Alzheimer’s is common, especially at its early stages and among the elderly, when its symptoms are mistaken to be the ‘typical cognitive decline’ that often comes with aging.
Diagnostic features currently include tests that assess mental abilities known as ‘cognitive assessments’ (e.g. memory tests). The individual is given a score which indicates the likelihood of Alzheimer’s disease being present. It is important to note that there is not a certain score that suggests a definite diagnosis of Alzheimer’s.
Brain imaging is also used as a co-diagnostic tool, but currently the only definitive method of confirming a diagnosis is examining the brain microscopically after the individual has passed away. Early diagnosis would allow for more adequate care for patients at early stages of Alzheimer’s.
In order to do this, we need to build upon what we already know about how this disease works. A healthy brain performs its functions via a complex network of interconnected nerve cells.
Neurons (nerve cells) are able to communicate vast and varied information (e.g. emotions, memories, thoughts, actions etc.) between one another by sending neurotransmitters (‘blobs’ secreted from nerve cells) across a gap between them (a synapse).
There are over 100 billion neurons and 100 trillion synapses and our brains have the incredible capacity to have many of them being activated and deactivated constantly for different reasons and with different levels of intensity. This sheer vastness also sheds light on the severity of diseases caused by the smallest neuronal dysfunction.
The main brain changes we are aware of in Alzheimer’s disease are the presence of amyloid plaques and neurofibrillary tangles.
Amyloid-beta precursor proteins are vital for neural growth and repair. Unfortunately, sometimes these proteins can break down and clump together forming ‘amyloid plaques’.
These plagues sit in between synapses, disrupting communication between neurons (the bowling games). With an amyloid plaque stuck in the synapse, the neurotransmitter cannot pass the message from one neuron to another.
Neurofibrillary tangles occur within nerve cells. They are caused by the build up of a protein known as ‘tau’ inside the cell. In healthy cells, there are tiny tubes (‘microtubules’) that allow nutrients to be passed from the cell body of a neuron to its long, winding extremities (dendrites).
These microtubules require tau protein to be stationary, like training wheels when you don’t quite know how to ride a bike yet. In Alzheimer’s, tau proteins bind to each other instead of the microtubules. This binding further progresses and these proteins weave themselves in and out of each other until they form complex ‘tangles’ that block the transport system within the cell3.
Emerging evidence has indicated that plaque build-up could lead to or affect the rapid accumulation of tau in the brain neurons. Most likely there is complex interplay involved between the two. A more straightforward way to grasp this would be to think about the collective breakdown of multiple vehicles on a motorway4.
Microglia in Alzheimer’s
The presence of molecules that are not supposed to be in our bodies activate our defence - the immune system. In response to build-up of amyloid plaques and tau proteins, our immune system releases a team of soldiers known as microglia which try to clear the dead and dying cells in the brain.
If microglia do not succeed - which unfortunately is often the case - the brain becomes inflamed. Inflammation then leads to further brain cell death and a decrease in brain volume, further compromising an individual’s ability to function due to significant breakdown in neuronal networks at later stages of disease5,6.
Signs and symptoms
This disease has many manifestations but is generally characterised by memory loss, agitation and change in personality such as paranoia. Alzheimer’s can be split into 3 broad stages:
Stage 1: preclinical Alzheimer’s disease where the brain is being damaged but there are no symptoms;
Stage 2: mild cognitive impairment due to Alzheimer’s where mild symptoms are present but do not affect everyday life and;
Stage 3: dementia due to Alzheimer’s disease which is further categorised into three stages.
- mild (e.g. forgetting important dates, dates or recently learned information),
- moderate (e.g. requiring assistance of daily living activities like dressing and bathing),
- severe (requiring 24 hour care, as physical symptoms become more prominent i.e. damage to the movement part of the brain causes the individual to become bed-bound).
Severe Alzheimer’s disease can be fatal with issues like aspiration pneumonia (difficulty swallowing that could lead to food particles being deposited in the lungs causing a dangerous infection) or blood clots due to being bed-bound.
Can Alzheimer’s disease be reversed?
At the moment, no. However, this ‘no’ does not come without hope. The scientific community has and still is continuing to follow in the steps of Alois Alzheimer who advocated for identifying biological causes for psychological diseases - we continue to question and build upon the research that has been paved before us.
Currently, there is no effective treatment for reversing progression of Alzheimer’s. The current drugs decrease severity of symptoms by improving cognitive ability in the earlier stages (no effective treatment for later stages of Alzheimer’s dementia).
Very recently, the first drug in almost 20 years has been approved by the US Food and Drug Administration called aducanumab (still in its phase 4 trial period, meaning patients who take it are monitored regularly) which works by clearing the buildup of plaque in the brain. However, its introduction has sparked controversy, as members of the scientific community have questioned the validity of the data from earlier clinical trials5.
Future research should work to answer this question and many others that follow: is there a biological change we can spot in those in the earlier stages that we can use to make better treatment or uncover more about the disease? What makes some individuals decline faster than others? Is there a method of diagnostic testing that allows for a minimally invasive deep investigation?
Risk factors: modifiable and unmodifiable
We have all heard the saying ‘prevention is better than cure’. While we still do not know as much as we would like about Alzheimer’s, we are aware of certain issues that may increase the risk of getting this disease.
There are two types of risk factors: modifiable and unmodifiable; factors that are under our control and factors that are not. Unmodifiable risk factors include: family history, age, ethnicity and genetic mutations.
While the unmodifiable factors are essentially our individual ‘baseline risk’, there are others that can be modified to help reduce our risk of Alzheimer’s. These modifiable risk factors are also known as lifestyle factors.
Some of these relating to Alzheimer’s include: heart and vessel health (if your arteries are clogged, less blood travels to the brain therefore increasing the likelihood of brain plaque formation), social and cognitive engagement. There are others that potentially have an impact on the risk of developing the disease currently being studied for example: sleep/sleep quality, alcohol use, depression and hearing impairment7.
- Dementia [Internet]. [cited 2021 Dec 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia
- How does the brain work? [Internet]. 2018 [cited 2021 Dec 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279302/
- Ma R-H, Zhang Y, Hong X-Y, Zhang J-F, Wang J-Z, Liu G-P. Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease. J Huazhong Univ Sci Technology Med Sci. 2017 Jun;37(3):307–12.
- Busche MA, Hyman BT. Synergy between amyloid-β and tau in Alzheimer’s disease. Nat Neurosci. 2020 Oct;23(10):1183–93.
- Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer’s disease. J Cell Biol. 2018 Feb 5;217(2):459–72.
- Sarlus H, Heneka MT. Microglia in Alzheimer’s disease. J Clin Invest. 2017 Sep 1;127(9):3240–9.
- A Armstrong R. Risk factors for Alzheimer’s disease. Folia Neuropathol. 2019;57(2):87–105.
- Lim MM, Gerstner JR, Holtzman DM. The sleep-wake cycle and Alzheimer’s disease: what do we know? Neurodegener Dis Manag. 2014;4(5):351–62.
- Stern Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol. 2012 Nov;11(11):1006–12.
- Colangeli S, Boccia M, Verde P, Guariglia P, Bianchini F, Piccardi L. Cognitive Reserve in Healthy Aging and Alzheimer’s Disease: A Meta-Analysis of fMRI studies. Am J Alzheimers Dis Other Demen. 2016 Aug;31(5):443–9.