LETTERS TO THE EDITOR
Case of progressive supranuclear palsy detected by tau
imaging with [
F]THK-5351 before the appearance of
characteristic clinical features
Progressive supranuclear palsy (PSP) has been recog-
nized as a rare cause of degenerative dementia in older
adults in recent times. PSP is a clinical syndrome com-
prising supranuclear palsy, postural instability and mild
dementia. The importance of the accurate identiﬁcation
of patients with PSP lies particularly in the management
of its characteristic symptoms. Furthermore, PSP is
characterized by deposition of four-repeat tau isoforms
in neuronal and glial inclusions.
As is generally
known, PSP has various clinical phenotypes.
fore, initial symptoms of PSP are various, and early
diagnosis of PSP is often difﬁcult in the daily clinical
setting. A recent study reported that tau imaging
positron-emission tomography (PET), speciﬁcally [
THK-5351 PET, can potentially be used to detect the
regional brain distribution of tau lesions in PSP.
We report a patient with PSP detected by [
5351 PET before the appearance of characteristic
clinical features. The patient was a 71-year-old right-
handed woman. Amnesic symptoms progressed from
3 years before consultation. The Mini-Mental State
Examination score was 19 out of 30 points at that time.
According to the detailed medical history, the main
complaint proved to be a language problem. She
required substantial effort in speech production, and
her spontaneous speech was non-ﬂuent. Neurological
examination showed no extrapyramidal signs, postural
instability or supranuclear gaze palsy. We scheduled
further examination for the patient whose condition
was primary progressive aphasia.
Among characteristic ﬁndings of PSP on magnetic
resonance imaging, only atrophy of the midbrain was
observed. No superior cerebellar peduncle and no dila-
tation of the third ventricle were observed. [
5351 and [
C]PIB PET scans were obtained 5 months
after the ﬁrst visit. No remarkable retention of [
PIB was observed in the neocortex. [
PET imaging showed a signiﬁcantly high retention in
the midbrain, left dominant frontal cortices and ante-
rior temporal lobe (Fig. 1).
Two months after the scans, the patient experienced
a gradual worsening in balance and started having falls.
She sustained a distal radius fracture 7 months after
the ﬁrst visit. Five months after the scans, vertical gaze
palsy appeared and the patient’s condition was diag-
nosed as PSP-Richardson syndrome (PSP rating scale:
) at 10 months after the ﬁrst visit, and the condition
of the ﬁrst visit was PSP-progressive non-ﬂuent
Four-repeat tauopathy, PSP and corticobasal degen-
eration, are the most common causes of the non-ﬂuent/
agrammatic variant of primary progressive aphasia.
Therefore, we have to consider four-repeat tauopathy if
the patient’s initial symptom was non-ﬂuent aphasia.
Unfortunately, the present case was not pathologically
conﬁrmed by autopsy. However, the patient’s eventual
condition was PSP-Richardson syndrome. Furthermore,
the accumulation pattern was different from corticoba-
sal degeneration, which has already been reported.
Therefore, we clinically diagnosed the patient as PSP.
Certainly, pathological conﬁrmation is required.
Tau imaging PET tracer has many regions of “off-tar-
get” bindings. Recently, it has become clear that not
only the distribution of tau has been detected.
THK-5351 binding to monoamine oxidase B has been
Furthermore, in AV 1451, binding to calci-
ﬁcation, iron, melanin and blood vessels are well known.
Relationships with neurodegeneration and inﬂamma-
tion have been reported for monoamine oxidase B. Even
if there is “off-target” binding to monoamine oxidase B
F]THK-5351, conﬁrmation of its distribution in
neurodegenerative diseases is considered to be rather
advantageous. Further studies with large samples, with
consideration of the results of pathological examina-
tions, are required to conﬁrm the present results.
In conclusion, it is possible that [
PET imaging can detect four-repeat tauopathy before
characteristic features of PSP appear.
We thank H Hirose of the Department of Nuclear
Medicine of Tokyo Medical University for his support
and technical assistance. We are also grateful to the
medical editors of the Department of International
Medical Communications of Tokyo Medical University
doi: 10.1111/ggi.13229 |© 2018 Japan Geriatrics Society
Geriatr Gerontol Int ; 18: 501–515