Reston,
VA (February 24, 2026)--A novel quantitative PET- and MRI-based imaging approach
can objectively identify a recently recognized type of dementia--limbic-predominant
age-related TDP-43 encephalopathy, or LATE--that is often mistaken as
Alzheimer's disease. This research, published online in The Journal of
Nuclear Medicine, may enable earlier differentiation of LATE and
Alzheimer's disease, or their co-existence in the clinic, guiding targeted
diagnostic work-up and personalized care for dementia patients.
LATE is a distinct neurodegenerative disorder
in older adults that manifests as memory-related cognitive decline closely
resembling Alzheimer's disease. It has attracted significant attention from
clinicians and investigators because of its high prevalence among elderly
people. Whereas Alzheimer's disease is closely associated with the accumulation
of amyloid and tau proteins, LATE is characterized by TDP-43 inclusions in the
limbic system.
"The distinction in the causes of these types
of dementia is critical, especially in the era of anti-amyloid therapies," said
Satoshi Minoshima, MD, PhD, FSNMMI, professor of Radiology and Imaging Sciences
at the University of Utah in Salt Lake City. "Because LATE has a different
underlying pathology and a seemingly different prognosis, it cannot be
diagnosed or treated in the same way as Alzheimer's disease."
Currently, LATE can only be definitively distinguished from Alzheimer's disease
through postmortem neuropathology. Because no clinically approved biomarker is
available to identify LATE--although efforts are underway to develop such
biomarkers-- physicians rely on a diagnostic framework that focuses on PET, MRI,
and clinical assessment.
"This has resulted in a significant gap in the
diagnosis and management of LATE," stated Minoshima. "Our study aimed to
introduce a quantitative diagnostic framework using commonly available imaging
tests to identify LATE, which can be applied in clinics with limited access to
advanced biomarkers."
In the study, researchers created stereotactic surface projections (3D-SSP) PET
templates from autopsy-confirmed datasets for LATE
neuropathologic change and Alzheimer's disease neuropathologic change. Next, z
score maps were generated from the autopsy-confirmed PET templates.
Using the autopsy-derived z score
maps, z score product indices were generated for 944 18F-FDG
PET cases that were referred from cognitive disorder
clinics in a tertiary care center. Patients were grouped into probable LATE,
probable LATE and Alzheimer's disease, and probable Alzheimer's disease groups.
Clinical and quantitative MRI volumetry data were then compared across the
groups.
Of the 944 consecutive clinical cases, 13
percent were characterized as probable LATE (2.4 percent pure LATE and 10.6
percent LATE and Alzheimer's disease) and 23.7 percent were characterized as
probable Alzheimer's disease without LATE. MRI volumetry revealed that the
medial temporal lobe was most affected in pure LATE cases, whereas the
orbitofrontal gyrus and lateral temporal lobe were most vulnerable in mixed LATE
and Alzheimer's disease cases. LATE and Alzheimer's disease related changes did
not appear to occur independently; rather, the same hemisphere tended to be
involved in both LATE and Alzheimer's disease within the same subject, possibly
indicating pathogenic synergy between these two conditions.
"The imaging patterns identified on PET and
MRI in this study provide clinicians with a practical tool to detect potential
LATE pathology in patients with cognitive impairment and to inform clinical
management and future investigations of LATE," noted Minoshima. "These efforts
will ultimately advance precision diagnostics and treatment stratification in
molecular imaging and nuclear medicine."