PRESS RELEASE
October 30, 2020
Brain imaging for early detection of Alzheimer’s disease and other dementias
Researchers at QST in Japan have developed a new imaging agent that allows early
detection and differentiation of various types of dementias, including Alzheimer’s disease
and frontotemporal lobar degeneration disorders

Chiba, Japan — As aging populations rise globally, so too do the numbers of people withdementia. Now more than ever, precise diagnosis and differentiation of Alzheimer’s
disease and other dementing illnesses is critical. A team of researchers led by MakotoHiguchi at the National Institutes for Quantum and Radiological Science and Technology(QST) in Japan has developed a new imaging probe that can be used for positron emission
tomography (PET) of brain pathologies characteristic of these diseases, allowing
identification of different types of dementias from an early stage.
Alzheimer’s disease and a large subset of frontotemporal lobar degeneration disorders(FTLD) are characterized by the accumulation of abnormal fibrils composed of tau
proteins in the brain. Without examining the brain pathology, accurate diagnosis of thesedementias is difficult, especially at the earliest stage because they share many overlapping
cognitive and behavioral symptoms. Within the brain, each of these dementias isassociated with the deposition of tau aggregates with a specific structure in uniquelocations.
PET imaging of tau pathologies in the brains of living subjects could therefore be bothclinically and scientifically of great utility. “Although good PET probes exist for
Alzheimer’s disease, they do not work well for other types of tau-positive dementias,”
says Higuchi.

PET scans rely on the ability of a radioligand to bind to the target molecules, in this case,the fibrillary form of tau proteins. Tau assemblies in Alzheimer’s disease and FTLD
syndromes are structurally distinct from each other, and most currently available PET
imaging agents have strong reactivity with tau deposits of AD type but not FTLD type.
The QST research group previously generated a PET probe, PBB3, for capturing diverse
tau pathologies, but it did not yield high contrast for tau aggregates in the brain due to its
propensity to metabolic degradations after systemic injection. In their new study, theresearchers at QST modified the PBB3 probe so that it was less susceptible to being
metabolized.
The new probe, PM-PBB3, is a longer-lasting and stable probe that produces strong
signals in the brain, enabling visualization of pathological tau protein species with highcontrast and dynamic range. The probe was tested in patients with Alzheimer’s disease
and FTLD disorders, including progressive supranuclear palsy, corticobasal degeneration,
and Pick’s disease, providing the first demonstration of high-contrast imaging of tau
accumulations in all these dementing illnesses. According to the distribution of tau
depositions detected by PM-PBB3, the researchers could identify and classify the taupositive dementias even at an early clinical stage of the disease, and the accuracy of thistest was proven by performing biopsy and autopsy in several cases who had undergone
PET scans.

PET imaging with 18F-PM-PBB3 (18F-APN-1607)

Because tau pathology begins before cognitive symptoms appear, the new probe should
facilitate the diagnosis of dementias at preclinical and prodromal stages. “In hospitals
equipped with PET scanners, our new radioligand could be practically useful for early
diagnosis or accurate typing of various dementias,” says the first author Kenji Tagai, also
from QST. “Additionally, PET with PM-PBB3 could be used for nonclinical and clinicaltests for candidate anti-tau therapeutics, as this technology is applicable to animal models
and humans.”
The researchers now hope to use their imaging technique as a reference for thedevelopment of a blood-based biomarker for dementias, which would allow efficient andinexpensive early detection at regular health check-ups, followed by more precise anddetailed workups using PET.

Paper
"High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and
Non-Alzheimer’s Disease Tauopathies”“Neuron”: October 29, 2020, doi: https://doi.org/10.1016/j.neuron.2020.09.042
Link (Publication)
Kenji Tagai1,2, Maiko Ono1, Manabu Kubota1,3, Yuhei Takado1, Makoto Higuchi1,Hitoshi Shimada1 et al.
1 National Institute of Radiological Sciences, QST
2 Department of Psychiatry, The Jikei University Graduate School of Medicine
3 Department of Psychiatry, Kyoto University Graduate School of Medicine

About QSTThe National Institutes for Quantum and Radiological Science and Technology (QST) was establishedin April 2016 to promote quantum science and technology in a comprehensive and integrated manner.
The new organization was formed from the merger of the National Institute of Radiological Sciences(NIRS) with certain operations that were previously undertaken by the Japan Atomic Energy Agency(JAEA).
QST’s mission is to raise the level of quantum and radiological sciences and technologies through its
commitment to research and development into quantum science and technology, the effect of radiation
on humans, radiation emergency medicine, and the medical use of radiation.
To ensure that research and development delivers significant academic, social and economic impacts,
and to maximize benefits from global innovation, QST is striving to establish world-leading researchand development platforms, explore new fields, and serve as a center for radiation protection andradiation emergency medicine.

•••Author Contact:
MAKOTO Higuchi, M.D., PhD
Department of Functional Brain Imaging
National Institute of Radiological Sciences, QST
Tel: +81-43-206-4700
Email: higuchi.makoto@qst.go.jp
Media Contact:
Public Relations Section
Department of Management and Planning, QST
Tel: +81-43-206-3026
Email: info@qst.go.jp
Website: https://www.qst.go.jp/site/qst-english/###