Vitreous STMN2 levels reflect TDP-43-associated neurodegeneration in postmortem eyes and brains

Surya V Pulukuri; Elizabeth E Spurlock; Fatima Tuz-Zahra; Yorghos Tripodis; Konstantina Sampani; Raymond Nicks; Gaoyuan Meng; Victor E Alvarez; Ann C McKee; Weiming Xia; Daniel A Mordes; Manju L Subramanian; Thor D Stein

doi:10.1177/25424823251392553

Vitreous STMN2 levels reflect TDP-43-associated neurodegeneration in postmortem eyes and brains

J Alzheimers Dis Rep. 2025 Oct 29:9:25424823251392553. doi: 10.1177/25424823251392553. eCollection 2025 Jan-Dec.

Authors

Surya V Pulukuri¹, Elizabeth E Spurlock², Fatima Tuz-Zahra³, Yorghos Tripodis^{2

3}, Konstantina Sampani^{4

5}, Raymond Nicks², Gaoyuan Meng⁶, Victor E Alvarez^{2

7

8}, Ann C McKee^{2

7

8}, Weiming Xia^{2

6}, Daniel A Mordes⁹, Manju L Subramanian^{10

11}, Thor D Stein^{2

7

8

12}

Affiliations

¹ Harvard Medical School, Boston, MA, USA.
² Alzheimer's Disease Research Center and CTE Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
³ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴ Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA.
⁵ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁶ Geriatric Research Education and Clinical Center, VA Bedford Healthcare System, Bedford, MA, USA.
⁷ VA Boston Healthcare System, Boston, MA, USA.
⁸ VA Bedford Healthcare System, Bedford, MA, USA.
⁹ Institute for Neurodegenerative Diseases, University of California, San Francisco, CA, USA.
¹⁰ Department of Ophthalmology, Boston Medical Center, Boston, MA, USA.
¹¹ Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
¹² Department of Pathology and Laboratory Medicine, Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

Abstract

Stathmin-2 (STMN2) levels decline in brains with transactive response DNA binding protein-43 (TDP-43) inclusions. TDP-43-related changes could extend to ocular structures, although vitreous STMN2 levels remain uncharacterized. This exploratory study analyzed 72 post-mortem brains and eyes depending on the presence or absence of TDP-43 inclusions in the brain and across neuropathological diagnostic groups (Alzheimer's disease [AD], chronic traumatic encephalopathy [CTE], AD and CTE, or neither). Results showed decreased vitreous STMN2 levels in TDP-43-positive cases but no association with diagnostic groups. Vitreous STMN2 was correlated with vitreous neurofilament light chain. Diminished vitreous STMN2 levels might indicate TDP-43-associated neurodegeneration.

Keywords: Alzheimer's disease; TDP-43; chronic traumatic encephalopathy; vitreous biomarkers.