Background
‐ Four-repeat (4R)-tauopathies include progressive
supranuclear palsy (PSP), corticobasal degeneration
(CBD), argyrophilic grain disease (AGD), globular glial
tauopathies (GGT), and FTLD-4R tau due to MAPT
mutation.
‐ These pathologies are associated with various and
overlapping clinical phenotypes, including
frontotemporal dementias (FTD), Alzheimer’s disease
(AD), and Lewy body diseases (LBD).
‐ Variable presentations may be differentially affected
by sex and co-pathologies.

Methods
National Alzheimer’s Coordinating Center for 536
individuals (253 females, 283 males) with pathologically
defined 4R-tauopathy:
‐ PSP: 77 females, 98 males
‐ CBD: 50 females, 64 males
‐ AGD: 114 females, 116 males
‐ Other 4R-tauopathy: 33 females, 34 males
Sex differences assessed with generalized linear models
in overall cohort and groups for
‐ co-pathologies (FTLD-3R tau, TDP-43, amyotrophic
lateral sclerosis/motor neuron disease, other FTLD,
hippocampal sclerosis, ischemic/hemorrhagic/vascular
pathology, aging-related tau astrogliopathy, AD
pathology [Thal score, Braak stage, CERAD neuritic
and diffuse plaque scores], Lewy body pathology,
substantia nigra neuron loss, cerebral amyloid
angiopathy) correcting for age at death
‐ clinical diagnoses, behavioral, motor symptoms and
onset age correcting for age at last visit,
‐ cognitive symptoms and onset age correcting for age
at last visit and education

Results
In general, females (F) were less likely to have cognitive decline, apathy, and motor
symptoms; and were older at cognitive and behavioral symptom onset than males (M).

Most common clinical diagnosis for both females and males were PSP for PSP group,
unspecified FTD for CBD group, AD for AGD & Other 4R groups

Conclusions
‐ Co-pathologies and clinical phenotypes may differ by sex for people with 4R
tauopathies.
‐ Females had a clinical advantage with less symptoms and later onset.
‐ Males had more frequent chronic traumatic encephalopathy, worse Lewy body
pathology, higher likelihood of LBD phenotype with Lewy body pathology.