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Background <p>Four-repeat (4R)-tauopathies cause variable clinical profiles leading to clinical misdiagnosis. While sex differences are reported in Alzheimer’s disease (AD), Lewy body disease (LBD), and clinically-defined frontotemporal dementia (FTD), little is known in 4R-tauopathies.</p> Methods <p>National Alzheimer’s Coordinating Center data were used for pathologically-defined 4R-tauopathies: progressive supranuclear palsy (PSP, <i>n</i> = 175), corticobasal degeneration (CBD, <i>n</i> = 114), argyrophilic grain disease (AGD, <i>n</i> = 230), Other-4R (<i>n</i> = 67). Sex differences for clinical presentation and co-pathologies were assessed adjusting for age and multiple comparisons.</p> Results <p>Most common clinical diagnosis was PSP (41%) for PSP; unspecified FTD (36%) for CBD; AD for AGD (57%) and Other-4R groups (48%), without sex differences. Females had less cognitive decline, apathy, motor symptoms; were older at cognitive, behavioral change onset. Males were more likely to demonstrate LBD co-pathology and clinical profile.</p> Conclusion <p>Both females and males have low clinical diagnostic accuracy for 4R-tauopathies. Females with 4R-tauopathies may experience less severe clinical presentations and less co-pathology.</p>

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Sex differences for clinical presentations and co-pathologies in four-repeat tauopathies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月3日

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  • Ece Bayram,
  • Danelle J. Carter,
  • Sana Aslam,
  • Emily Forbes,
  • Samantha K. Holden

摘要

Background

Four-repeat (4R)-tauopathies cause variable clinical profiles leading to clinical misdiagnosis. While sex differences are reported in Alzheimer’s disease (AD), Lewy body disease (LBD), and clinically-defined frontotemporal dementia (FTD), little is known in 4R-tauopathies.

Methods

National Alzheimer’s Coordinating Center data were used for pathologically-defined 4R-tauopathies: progressive supranuclear palsy (PSP, n = 175), corticobasal degeneration (CBD, n = 114), argyrophilic grain disease (AGD, n = 230), Other-4R (n = 67). Sex differences for clinical presentation and co-pathologies were assessed adjusting for age and multiple comparisons.

Results

Most common clinical diagnosis was PSP (41%) for PSP; unspecified FTD (36%) for CBD; AD for AGD (57%) and Other-4R groups (48%), without sex differences. Females had less cognitive decline, apathy, motor symptoms; were older at cognitive, behavioral change onset. Males were more likely to demonstrate LBD co-pathology and clinical profile.

Conclusion

Both females and males have low clinical diagnostic accuracy for 4R-tauopathies. Females with 4R-tauopathies may experience less severe clinical presentations and less co-pathology.