Alzheimer’s patients divided into 5 subgroups, potentially enabling ‘personalized medicine,’ study finds


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Researchers have identified a total of five subgroups among Alzheimer’s patients, according to a new study published in the journal Nature Aging on Jan. 9.

Different groups may require different treatment options, as noted in a press release from Alzheimer Center Amsterdam, Amsterdam UMC and Maastricht University.

“Previously, it was thought that Alzheimer’s disease is one disease, and that treatments being developed will work similarly for all individuals,” lead researcher Betty Tijms, associate professor of neuroscience and brain imaging at Amsterdam UMC, told Fox News Digital in an email.

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“We found that patients with Alzheimer’s disease differ in the biological processes involved — which means that possibly treatments will only work for a subgroup of patients.”

In the study, the researchers analyzed 1,058 proteins in the cerebrospinal fluid of 419 people with Alzheimer’s disease from studies at the Alzheimer Center Amsterdam.

Researchers have identified a total of five subgroups among Alzheimer’s patients, according to a new study published in the journal Nature Aging. Different groups may require different treatment options.  (iStock)

They identified five different variants, according to the release describing the findings.

The first group had increased amyloid production in the brain, which results in a buildup of plaques that impede cognitive function, a hallmark of Alzheimer’s.

“This may explain why some patients respond better to some treatments.”

A second group was found to have a disruption in the blood-brain barrier, reduced amyloid production and less growth of nerve cells

The remaining groups showed differences in protein synthesis, immune system function and cerebrospinal fluid production, the researchers noted.

Some of the groups were found to have faster progression of symptoms than others.

Brain scans

In the study, the researchers (not pictured) analyzed 1,058 proteins in the cerebrospinal fluid of 419 people with Alzheimer’s disease from studies at the Alzheimer Center Amsterdam. (iStock)

In an earlier, smaller study, the researchers found three subtypes (aberrant neuroplasticity, innate immune activation and blood-brain barrier dysfunction), Tijms noted. 

“In our new, larger dataset, we again found those three subtypes, but also two new subtypes, with underlying processes that we did not expect to find beforehand,” she said. 

One of those new subtypes was rare, including only 6% of the patients — but it had the worst disease prognosis, the researcher said. 

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“This subtype had problems with protein synthesis,” she said. “The other subtype had impairment of the choroid plexus, which is the organ in the brain that produces cerebrospinal fluid.”

The study did have some limitations, the researchers acknowledged.

“While we expect that subtypes may have different response to treatment, we were not yet able to demonstrate this, because we need access to cerebrospinal fluid samples from existing drug trials,” noted Tijms. 

“We hope to test this in future studies.”

Alzheimer's patient - brain scans

Based on the new findings about Alzheimer’s, treatment response and side effects could differ between patients from different subtypes, the researchers said. (iStock)

Additionally, the study was performed among relatively young patients, with an average age of 66 years.

“Subtypes may be different at older ages, as the majority of patients with AD are 80 years and older),” Pieter Jelle Visser, associate professor of neuroscience at Amsterdam UMC, told Fox News Digital.

Based on these findings, researchers involved in treatment development should take into account that treatment response and side effects could differ between patients from different subtypes, Visser noted. 

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“For example, they could define the subtypes of patients to identify the ones who best respond to the trial,” he said. “This could also be done with samples that already have been collected in previous trials.”

Researchers could also test novel treatments only in a subtype that is likely to respond to the treatment, Tijms added, such as testing immune treatment in the subtype with immune activation.

Couple with doctor

“Each subgroup may need its own treatment, or version of a treatment, or combination of treatments, in order to be effective with the least side effects,” said a doctor from the Alzheimer’s Association. (iStock)

Dr. Kirk C. Wilhelmsen, professor of neurology and chief of cognitive neurology at West Virginia University Rockefeller Neuroscience Institute, said this research is an “important paper,” but noted that it’s not ready to be implemented in clinical practice.

Wilhelmsen was not involved in the study.

“This may explain why some patients respond better to some treatments,” he told Fox News Digital. “It may salvage some drugs that have failed in clinical trials.”

Medical researchers

Researchers said the hope is that the identification of these subgroups may salvage some drugs that have failed in clinical trials. (iStock)

Dr. Claire Sexton, senior director of scientific programs and outreach at the Alzheimer’s Association in Chicago, noted in a statement to Fox News Digital that while there are common brain changes that define Alzheimer’s, the experience of the disease varies from person to person.

“Now we are learning more about how some aspects of the biology of Alzheimer’s may also be different for different patients,” said Sexton, who was also not a participant in the Amsterdam research.

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“This includes differences in symptoms, the speed of progression and response to treatments,” she went on. 

“Research that gives us a better understanding of the biology of Alzheimer’s disease can … inform therapeutic possibilities and drug development, and may advance the field toward personalized medicine approaches.”

A PET scan in Washington, D.C.

A patient who suffers from Alzheimer’s is shown preparing to receive a PET scan at MedStar Georgetown University Hospital in Washington, D.C., on June 20, 2023.  (Michael Robinson Chávez/The Washington Post via Getty Images)

If these subtypes are validated and confirmed, Sexton said, they may help to explain why some individuals do or do not respond to certain treatments, or experience different types and severity of side effects.

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“Each subgroup may need its own treatment, or version of a treatment, or combination of treatments, in order to be effective with the least side effects,” she said.

To confirm these findings, Sexton called for additional research with larger study groups that “accurately represent the diversity of the at-risk and affected populations.”

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