Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that damages brain cells and causes problems with memory, behaviour and thinking. This is the most common type of dementia with symptoms usually developing slowly and getting worse over time, until carrying out the simplest tasks becomes impossible.

AD develops slowly initially involving the parts of the brain that control memory and language. Although the process and damage most often begin years before, the early symptoms become apparent usually when people are in their sixties and seventies. These may include forgetting recent events or conversations. Later on, other symptoms can appear, like trouble focusing and communicating, feeling disoriented, confused or anxious, experiencing dramatic mood swings. Eventually, people with AD will develop severe memory impairment, fail to perform everyday activities and will require total care. The two types of the disease are: early-onset AD (< age 65) often has a genetic background and late-onset Alzheimer’s disease, which is most common (> age 65).

Although the exact causes of the disease are not fully understood yet, scientists believe that for most people, it is caused by a combination of genetic, lifestyle and environmental factors. Essentially, there are problems with proteins in the brain that fail to function normally which leads to nerve cell death and tissue loss throughout the brain.

Until recently, research has focused mainly on two aspects:

• Plaques. Beta-amyloids (A-beta) are leftover fragments of larger proteins and are broken down and eliminated in a healthy brain. However, in people with AD they form hard, insoluble accumulations that clump together between nerve cells and block cell-to-cell signalling. Plaques can be linked to a protein called ApoE, which transports cholesterol in the blood. A-beta plaques may also activate immune system cells that trigger inflammation.
• Tangles. Tau proteins have an important role inside neurons as part of microtubules in carrying nutrients and other essential materials. In AD, tau proteins have abnormal shape and form neurofibrillary tangles. The tangles disrupt microtubule structures and the transport system and are toxic to cells.

As AD is a complex and multifactorial disease, in recent years the focus of research has shifted to explore a broader range of possible causes, and scientists no longer study the brain in isolation but as part of a wider context. Amongst others, it is now investigated whether AD might be a systematic disease connected to metabolic dysfunction or vascular and inflammatory factors. The role of NFAT signalling in Aβ-mediated neurodegeneration, the importance of GABA-upregulation in memory impairment, and newly identified genetic risk factors are also being extensively studied.

GLOBAL STATISTICS

In 2010, the number of cases of AD worldwide was already 30.8 million and is expected to increase over 106.2 million by 2050. About 1 in 8 people over the age of 65 is living with this disease which shows what a huge burden Alzheimer’s is to society. According to the 2019 Alzheimer’s Facts and Figures Report, the total cost associated with AD in 2019 is estimated at $280 billion in the US alone.

CURRENTLY AVAILABLE TREATMENT

Around one third of cases of AD worldwide can be related to numerous potentially modifiable risk factors. This means there are various lifestyle choices that may help delaying AD, including regular exercise, keeping a healthy diet, learning new things, and having strong social connections. However, there is no effective treatment yet that cures Alzheimer’s disease or alters the disease process. Current medications may only temporarily improve symptoms or slow disease progress. That is why novel, multi target treatment options are much needed.