Scientists have discovered that there are five types of Alzheimer’s disease, and this could explain why some medications appear to be ineffective against the condition.
Dutch experts came to this conclusion after examining the proteins in the cerebrospinal fluid, found in the brain and spinal column, of more than 400 Alzheimer’s patients.
When analyzing these proteins, they discovered important differences, splitting what was once a single condition into five different subtypes, with different clinical progression and life expectancy.
By identifying specific types of the disease, scientists hope they can develop targeted and therefore more effective treatments.
Alzheimer’s disease, a leading cause of dementia, is a progressive disease of the brain in which the buildup of abnormal proteins causes nerve cells to die.
Dutch experts have found five subtypes of Alzheimer’s disease after examining the proteins in the cerebrospinal fluid, found in the brain and spinal column, of more than 400 patients
This graph shows the brain areas that shrunk in each Alzheimer’s disease subtype in the study compared to healthy controls. Blue areas indicate shrinkage, with the deeper shades representing more extreme withdrawal, while pink areas indicate areas of greater thickness
As these cells die, the functions they provide are gradually lost, robbing people of their memory, orientation, and ability to think and reason.
There is no cure and people with Alzheimer’s disease will need more and more care as the disease progresses.
In the study, published in the journal Nature agingscientists from the Alzheimer Center Amsterdam, the University of Amsterdam and Maastricht University in the Netherlands examined 419 patients with Alzheimer’s disease.
They collected cerebrospinal fluid, a clear, colorless fluid found in the tissue surrounding the brain and spinal cord, and examined it for 1,058 proteins.
By comparing the results of the study cohort, they found five different subtypes of Alzheimer’s disease, each with potential clinical implications for their treatment.
One variant was found to cause an unusually high level of brain cell growth, stimulating production of the abnormal proteins that cause Alzheimer’s disease.
Patients with this subtype had the longest average life expectancy compared to other subtypes; they lived an average of nine years after diagnosis.
A second class of Alzheimer’s disease was caused by problems with the brain’s internal immune system, while a third variant was linked to problems with the brain’s protein production.
A fourth subtype was related to problems with blood flow to the brain, while a fifth subtype was activated problems with the blood-brain barrier, a cell barrier that normally prevents larger substances from reaching the delicate tissue of the brain.
Patients with the second and fourth variants had the greatest brain atrophy – when the brain loses neurons, leading to thinking and memory problems – MRI scan results revealed.
But patients with subtype three showed the worst progression of the disease, living on average only five and a half years after diagnosis.
Some of the proteins identified in each subtype were also linked to specific genes, meaning some people are naturally more susceptible to one type of Alzheimer’s.
The authors said the results may explain why some previously tested Alzheimer’s drugs failed or underperformed in clinical trials, despite promising results in the laboratory.
The theory goes that because each subtype appears to have a slightly different cause and composition of abnormal protein accumulation, medications may only work in some or one group of patients.
This not only affects drug effectiveness, but also safety, as several drugs can interact dangerously with some subtypes.
The authors wrote: ‘For example, although antibodies may more easily cross the blood-brain barrier in subtype 5, these individuals may be at increased risk of brain haemorrhage that can occur with antibody treatment.’
The researchers said their results highlighted the need for personalized treatments for Alzheimer’s patients.
Changes in humor and increased swearing are all signs of Alzheimer’s disease and frontotemporal dementia (FTD), a form of dementia that causes problems with behavior and language. According to experts, poor parking and shabby clothes are also signs of the memory-robbing disease. Graphic shows: six signs of Alzheimer’s disease
They also called for further research to reanalyze old clinical trials to test whether certain treatments may have specific benefits for specific Alzheimer’s subtypes.
Alzheimer’s disease is the leading cause of dementia, a condition in which people have a reduced ability to remember, think or make decisions, which interferes with daily activities.
Dementia affects 900,000 people in Britain and an estimated 7 million in the US.
The condition is considered a global health problem, with rates expected to explode as people live longer increasing pressure on healthcare systems.
According to Alzheimer’s Research UK, caring for patients with Alzheimer’s disease and dementia costs the UK an estimated £25 billion per year. The vast majority of the amount is spent on social care.
Some of the first signs that someone has Alzheimer’s disease include forgetting recent conversations or events, losing objects, forgetting the names of places and objects, trouble finding the right word, repeating asking questions, poor judgment and finding it more difficult to make decisions.
There is currently no cure for Alzheimer’s disease, but treatment instead focuses on relieving symptoms.
However, there have been some encouraging developments in the past year.
Trials in 2023 showed new drug donanemab can clear out the abnormal proteins that cause the disease, slowing the early progression of Alzheimer’s by as much as 60 percent, a breakthrough hailed as a ‘turning point’ in the fight against the disease.
Other researchers are working on a vaccine for Alzheimer’s disease, while other teams have conducted studies showing that zapping the brain with electricity twice a day can reduce symptoms.