September 21 was World Alzheimer’s Day, a neurodegenerative disease with a chronic and progressive course and the most common cause of dementia in the elderly population in developed countries. To date, an estimated 20% of those over the age of 85 and about 5% of the population over the age of 65 are affected. However, several early cases are recognised, in which the disease is onset before age 50.
Symptoms may vary among individuals but all fall within the spectrum of gradual loss of cognitive function, for example:
- Progressive memory loss, the most well-known symptom
- Difficulty with language
- Difficulty performing normal daily activities
- Loss of autonomy
- Spatial and temporal disorientation
Progressive exacerbation of symptoms may be accompanied by even substantial personality changes in the sufferer.
A disease difficult to understand
For decades, efforts in Alzheimer’s research have been aimed at understanding the underlying mechanisms of the disease.
One of the most relevant discoveries has been the correlation between genetics and Alzheimer’s disease. In 1984, the discovery of apolipoprotein Ɛ as a genetic risk factor led to a deeper understanding of the heritability of the disease. It was discovered that individuals with an alteration in the APOEƐ4 gene are at increased risk of developing Alzheimer’s. This discovery opened new avenues for research, including the study of genetic variants associated with the disease.
The current predominant theory on the origins of Alzheimer’s focuses on the involvement of two crucial proteins: beta-amyloid and tau. Beta-amyloid takes on different molecular conformations, aggregating between neurons. This protein originates from the fragmentation of a larger protein called amyloid precursor protein (APP). A specific form of beta-amyloid, known as beta-amyloid 42, is particularly harmful.
In the brains of people with Alzheimer’s disease, abnormal accumulations of this protein (also present in smaller amounts in healthy brains) occur, forming aggregates known as plaques. These plaques accumulate between neurons, impairing cell function and contributing to the cognitive impairment associated with the disease.
Significant steps forward that now give us a clearer picture of the disease and its course but are still not enough to arrive at a cure.
Current and future therapies for Alzheimer’s disease
Today, Alzheimer’s therapies are mainly aimed at managing symptoms and slowing the progression of the disease. For some patients, at a mild or moderate stage, there are drugs that can help limit the worsening of symptoms for a few months. These active ingredients work as inhibitors of acetylcholinesterase, an enzyme that destroys acetylcholine, the neurotransmitter deficient in the brains of Alzheimer’s patients.
The most fascinating aspect of Alzheimer’s research, however, is the new horizons that are opening up with biological therapies in development. Some researchers are exploring the use of monoclonal antibodies to remove beta-amyloid accumulations in the brain, considered a major cause of Alzheimer’s. These treatments are showing promising results in the early stages of clinical trials.
Another growing field involves gene therapies. Scientists are trying to develop therapies that can correct or mitigate genetic mutations that predispose to Alzheimer’s disease. This approach could represent a major breakthrough in preventing the disease.
In parallel, research is exploring nonpharmacological approaches. Deep brain stimulation, for example, has been tested to improve memory and cognitive function in some patients. The integration of digital technologies is also revolutionising Alzheimer’s diagnosis and monitoring: artificial intelligence-based applications and devices can analyse patients’ behavioural patterns to detect cognitive changes early. New discoveries in this field are steadily increasing, in fact becoming one of the most promising approaches to fighting Alzheimer’s.
Neurodegenerative diseases remain one of medicine’s great open challenges, but the progress of research and the work of brilliant minds around the world give us hope for a future in which these disorders become fully treatable.