Introduction: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy characterized by multiple clinicopathologic subtypes. Advanced neuroimaging techniques have shown an early ability to distinguish PSP subtypes noninvasively for improved diagnosis. This study utilized tau PET imaging and MRI techniques at 7T to determine the neuroimaging profile of a participant with comorbid PSP and amyotrophic lateral sclerosis (ALS). Method: [18F]-flortaucipir PET imaging was performed on one participant with PSP-ALS, one participant with typical PSP (Richardson’s syndrome; PSP-RS), and 15 healthy control volunteers. Standardized uptake value ratio (SUVR) in each brain region was compared between PSP participants and controls. Quantitative susceptibility mapping (QSM) and inflow-based vascular-space occupancy MRI at 7T were performed on the two PSP participants and on two age-matched healthy controls to evaluate for differences in regional brain iron content and arteriolar cerebral blood volume (CBVa), respectively. Results: In the participant with PSP-ALS, the precentral gyrus demonstrated the highest [18F]-flortaucipir uptake of all brain regions relative to controls (z-score 1.94). In the participant with PSP-RS, [18F]-flortaucipir uptake relative to controls was highest in subcortical regions, including the pallidum, thalamus, hippocampus, and brainstem (z-scores 1.08, 1.41, 1.49, 1.32, respectively). Susceptibility values as a measure of brain iron content were higher in the globus pallidus and substantia nigra than in the midbrain and pons in each participant, regardless of group. CBVa values tended to be higher in the subcortical gray matter in PSP participants than in controls, although large measurement variability was noted in controls across multiple regions. Conclusion: In vivo tau PET imaging of an individual with PSP-ALS overlap demonstrated increased tau burden in the motor cortex that was not observed in PSP-RS or control participants. Consistent with prior PET studies, tau burden in PSP-RS was mainly observed in subcortical regions, including the brainstem and basal ganglia. QSM data suggest that off-target binding to iron may account for some but not all of the increased [18F]-flortaucipir uptake in the basal ganglia in PSP-RS. These findings support existing evidence that tau PET imaging can distinguish among PSP subtypes by detecting distinct regional patterns of tau deposition in the brain. Larger studies are needed to determine whether CBVa is sensitive to changes in brain microvasculature in PSP.

1.
Höglinger
GU
,
Respondek
G
,
Stamelou
M
,
Kurz
C
,
Josephs
KA
,
Lang
AE
, et al
.
Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria
.
Mov Disord
.
2017
;
32
(
6
):
853
64
.
2.
Boxer
AL
,
Yu
JT
,
Golbe
LI
,
Litvan
I
,
Lang
AE
,
Höglinger
GU
.
Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches
.
Lancet Neurol
.
2017
;
16
(
7
):
552
63
.
3.
Whitwell
JL
,
Tosakulwong
N
,
Botha
H
,
Ali
F
,
Clark
HM
,
Duffy
JR
, et al
.
Brain volume and flortaucipir analysis of progressive supranuclear palsy clinical variants
.
Neuroimage Clin
.
2020
;
25
:
102152
.
4.
Lowe
VJ
,
Curran
G
,
Fang
P
,
Liesinger
AM
,
Josephs
KA
,
Parisi
JE
, et al
.
An autoradiographic evaluation of AV-1451 Tau PET in dementia
.
Acta Neuropathol Commun
.
2016
;
4
(
1
):
58
.
5.
Marquié
M
,
Verwer
EE
,
Meltzer
AC
,
Kim
SJW
,
Agüero
C
,
Gonzalez
J
, et al
.
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
.
Acta Neuropathol Commun
.
2017
;
5
(
1
):
75
.
6.
Gogola
A
,
Minhas
DS
,
Villemagne
VL
,
Cohen
AD
,
Mountz
JM
,
Pascoal
TA
, et al
.
Direct comparison of the tau PET tracers 18F-flortaucipir and 18F-MK-6240 in human subjects
.
J Nucl Med
.
2022
;
63
(
1
):
108
16
.
7.
Koga
S
,
Sanchez-Contreras
M
,
Josephs
KA
,
Uitti
RJ
,
Graff-Radford
N
,
van Gerpen
JA
, et al
.
Distribution and characteristics of transactive response DNA binding protein 43 kDa pathology in progressive supranuclear palsy
.
Mov Disord
.
2017
;
32
(
2
):
246
55
.
8.
Petrozziello
T
,
Amaral
AC
,
Dujardin
S
,
Farhan
SMK
,
Chan
J
,
Trombetta
BA
, et al
.
Novel genetic variants in MAPT and alterations in tau phosphorylation in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid
.
Brain Pathol
.
2022
;
32
(
2
):
e13035
.
9.
Choi
JY
,
Cho
H
,
Ahn
SJ
,
Lee
JH
,
Ryu
YH
,
Lee
MS
, et al
.
Off-target 18F-AV-1451 binding in the basal ganglia correlates with age-related iron accumulation
.
J Nucl Med
.
2018
;
59
(
1
):
117
20
.
10.
Golbe
LI
,
Ohman-Strickland
PA
.
A clinical rating scale for progressive supranuclear palsy
.
Brain
.
2007
;
130
(
Pt 6
):
1552
65
.
11.
Nasreddine
ZS
,
Phillips
NA
,
Bédirian
V
,
Charbonneau
S
,
Whitehead
V
,
Collin
I
, et al
.
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
.
J Am Geriatr Soc
.
2005
;
53
(
4
):
695
9
.
12.
Smith
GS
,
Protas
H
,
Kuwabara
H
,
Savonenko
A
,
Nassery
N
,
Gould
NF
, et al
.
Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment
.
Neuroimage Clin
.
2023
;
37
:
103322
.
13.
Hua
J
,
Lee
S
,
Blair
NIS
,
Wyss
M
,
van Bergen
JMG
,
Schreiner
SJ
, et al
.
Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-β-related cognitive decline
.
Neurobiol Aging
.
2019
;
76
:
181
93
.
14.
Chen
L
,
Hua
J
,
Ross
CA
,
Cai
S
,
van Zijl
PCM
,
Li
X
.
Altered brain iron content and deposition rate in Huntington’s disease as indicated by quantitative susceptibility MRI
.
J Neurosci Res
.
2019
;
97
(
4
):
467
79
.
15.
Mori
S
,
Wu
D
,
Ceritoglu
C
,
Li
Y
,
Kolasny
A
,
Vaillant
MA
, et al
.
MRICloud: delivering high-throughput MRI neuroinformatics as cloud-based software as a service
.
Comput Sci Eng
.
2016
;
18
(
5
):
21
35
.
16.
Li
X
,
Chen
L
,
Kutten
K
,
Ceritoglu
C
,
Li
Y
,
Kang
N
, et al
.
Multi-atlas tool for automated segmentation of brain gray matter nuclei and quantification of their magnetic susceptibility
.
Neuroimage
.
2019
;
191
:
337
49
.
17.
Baker
SL
,
Maass
A
,
Jagust
WJ
.
Considerations and code for partial volume correcting [18F]-AV-1451 tau PET data
.
Data Brief
.
2017
;
15
:
648
57
.
18.
Jin
J
,
Su
D
,
Zhang
J
,
Li
X
,
Feng
T
.
Tau PET imaging in progressive supranuclear palsy: a systematic review and meta-analysis
.
J Neurol
.
2023
;
270
(
5
):
2451
67
.
19.
Nihei
K
,
McKee
AC
,
Kowall
NW
.
Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients
.
Acta Neuropathol
.
1993
;
86
(
1
):
55
64
.
20.
Josephs
KA
,
Katsuse
O
,
Beccano-Kelly
DA
,
Lin
WL
,
Uitti
RJ
,
Fujino
Y
, et al
.
Atypical progressive supranuclear palsy with corticospinal tract degeneration
.
J Neuropathol Exp Neurol
.
2006
;
65
(
4
):
396
405
.
21.
Fu
YJ
,
Nishihira
Y
,
Kuroda
S
,
Toyoshima
Y
,
Ishihara
T
,
Shinozaki
M
, et al
.
Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity
.
Acta Neuropathol
.
2010
;
120
(
1
):
21
32
.
22.
Ahmed
Z
,
Bigio
EH
,
Budka
H
,
Dickson
DW
,
Ferrer
I
,
Ghetti
B
, et al
.
Globular glial tauopathies (GGT): consensus recommendations
.
Acta Neuropathol
.
2013
;
126
(
4
):
537
44
.
23.
Gawel
M
,
Jamrozik
Z
,
Szmidt-Salkowska
E
,
Slawek
J
,
Gawel
D
,
Rowińska-Marcińska
K
, et al
.
Electrophysiological features of lower motor neuron involvement in progressive supranuclear palsy
.
J Neurol Sci
.
2013
;
324
(
1–2
):
136
9
.
24.
Riku
Y
,
Iwasaki
Y
,
Ishigaki
S
,
Akagi
A
,
Hasegawa
M
,
Nishioka
K
, et al
.
Motor neuron TDP-43 proteinopathy in progressive supranuclear palsy and corticobasal degeneration
.
Brain
.
2022
;
145
(
8
):
2769
84
.
25.
Kovacs
GG
,
Lukic
MJ
,
Irwin
DJ
,
Arzberger
T
,
Respondek
G
,
Lee
EB
, et al
.
Distribution patterns of tau pathology in progressive supranuclear palsy
.
Acta Neuropathol
.
2020
;
140
(
2
):
99
119
.
26.
Pramstaller
PP
,
Marsden
CD
.
The basal ganglia and apraxia
.
Brain
.
1996
;
119
(
Pt 1
):
319
40
.
27.
Lemoine
L
,
Leuzy
A
,
Chiotis
K
,
Rodriguez-Vieitez
E
,
Nordberg
A
.
Tau positron emission tomography imaging in tauopathies: the added hurdle of off-target binding
.
Alzheimers Dement
.
2018
;
10
:
232
6
.
28.
Lee
JH
,
Lee
MS
.
Brain iron accumulation in atypical parkinsonian syndromes: in vivo MRI evidences for distinctive patterns
.
Front Neurol
.
2019
;
10
:
74
.
29.
Cogswell
PM
,
Fan
AP
.
Multimodal comparisons of QSM and PET in neurodegeneration and aging
.
Neuroimage
.
2023
;
273
:
120068
.
You do not currently have access to this content.