ARIA is associated with expansion of peripheral CD8⁺
TEMRA cells. Credit: Nature Communications (2026). DOI: 10.1038/s41467-026-68921-3
A team of University of Kentucky researchers has uncovered a surprising
clue in the battle against Alzheimer's disease that could help doctors predict,
and ultimately prevent, a common side effect of the newest generation of
Alzheimer's therapies. Their findings, recently published in Nature
Communications, reveal a distinct immune "fingerprint" in the
blood of patients who develop amyloid-related imaging abnormalities (ARIA)
after treatment with lecanemab—the first
Food and Drug Administration-approved drug shown to slow Alzheimer's disease
progression.
ARIA, which can show up as brain swelling or small bleeds on MRI scans, is
one of the biggest obstacles to broader use of the promising anti-amyloid
antibody therapies now becoming available. Before now, clinicians and families
have had little to go on to explain why some people develop these side effects
and others do not.
"We asked a simple question: do people who develop ARIA show a
different immune 'fingerprint' in their blood than those who don't? The answer
appears to be yes," said Josh Morganti, Ph.D., assistant professor of
neuroscience in the UK College of Medicine and researcher at the University of
Kentucky's Sanders-Brown Center on Aging.
Using advanced genetic and metabolic profiling on blood samples from
patients treated with lecanemab at Norton Neuroscience Institute in Louisville,
Morganti and colleagues found that people who developed ARIA had an expansion
of a specific type of immune cell—a subset of T cells—that was metabolically
"revved up" and poised for action.
"This isn't random noise. We're seeing a coordinated immune response
that distinguishes patients with ARIA at a biological level," he said.
Critically, the study shows that this signal can be detected in a simple
blood draw, not through invasive procedures.
"Until now, we really didn't understand why some people develop ARIA
and others don't," Morganti said. "And we can't biopsy someone's
brain to figure that out. This study shows that we can learn something
meaningful from the blood, which is an important step if we
ever want to turn these findings into a real-world screening tool."
Lance Johnson, Ph.D., associate professor of physiology and researcher at
Sanders-Brown, said the findings set the stage for a more personalized approach
to Alzheimer's care. "We now know that ARIA isn't just an imaging
artifact," Johnson said. "There's biology behind it that we can
measure. That means we have something to work with."
Before this research, the primary risk factor clinicians knew for ARIA was
genetic: Carriers of the APOE ε4 gene
variant were at higher risk. But what was happening biologically remained
mysterious. The UK team's work—the first in-depth look at the peripheral immune
system in ARIA patients—reveals that certain T cells expand, shift their
metabolism and express the molecular machinery needed to interact with the
vascular system.
"This suggests ARIA may have a biological signature we can detect in
the blood," said Johnson.
A path toward prediction and better treatment
The ultimate goal of this work is to make Alzheimer's immunotherapies safer
and more accessible. The immune signatures the UK researchers identified could,
after validation in larger patient groups, become the basis for a blood test to
flag individuals at higher risk before they begin treatment.
"If we can validate these findings in larger groups, clinicians
could adjust treatment—closer monitoring, different
dosing schedules or even targeted interventions—based on a patient's immune
profile," said Morganti. "For people and families facing an
Alzheimer's diagnosis, anything that makes these new treatments safer and more
accessible is meaningful."
Johnson agreed: "Right now, ARIA is a cloud hanging over these
otherwise groundbreaking therapies. If we can use this work to help predict or
even prevent these side effects, it will be a big step forward."
Both researchers emphasized that they are not there yet, but this study
pushes the field past guesswork into measurable biological terrain.
Collaboration, support and gratitude
The UK research team expressed their gratitude for the indispensable
contribution of Norton Neuroscience Institute and Norton Research Institute in
Louisville.
"I'm incredibly proud of the work our team has done to bring hope to
patients facing an Alzheimer's diagnosis," said Gregory E. Cooper, M.D.,
Ph.D., chief of adult neurology and director of the Norton Neuroscience
Institute Memory Center. "These findings have the potential to
significantly improve the safety and precision of care for patients undergoing
anti-amyloid therapy. This collaboration is a powerful example of what can be
achieved when experts unite around a shared purpose. I look forward to building
on this momentum as we continue advancing research and improving the lives of
those affected by Alzheimer's disease."
Both Johnson and Morganti agree that the collaboration exemplifies how
academic medical centers can extend their research through relationships with
community-based clinical programs.
"Lecanemab-treated patients represent a rare and difficult-to-access population," said Morganti. "Dr. Cooper and his team's energy and enthusiasm to collaborate—coordinating care and research sample collection during active treatment—made this work possible."
Provided
by University
of Kentucky
Source: Blood immune 'fingerprint' may help predict serious side effects of new Alzheimer's drug
No comments:
Post a Comment