My research is focused on translational research in Alzheimer’s disease and related dementias (ADRD), specifically in delineating the pathogenic mechanisms linking AD and other common neurodegenerative and vascular pathologies. My current research focus is on limbic-predominant age-related TDP-43 encephalopathy (LATE), a common brain pathology that causes amnestic dementia in the elderly. I am pursuing several lines of inquiry, including:

1. What is the pathogenic role of arteriolosclerosis in LATE?
2. What are the key differences between pure LATE and LATE + AD?
3. How do we definitively differentiate LATE from FTLD-TDP (frontotemporal lobar degeneration with TDP-43 lesions)?

My collaborative research involves:

• Developing biomarkers for early diagnosis of AD and differentiating AD from other tauopathies.
• Investigating the molecular mechanisms of differential AD susceptibility by spatial transcriptomic profiling. 

Publications

Shih-Hsiu J. Wang, Yuanyuan Guo, John F. Ervin, Jay B. Lusk, and Sheng Luo. “Neuropathological associations of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) differ between the oldest-old and younger-old ” Acta Neuropathol (in press) 
 
Liu, Andy J., Jay B. Lusk, John Ervin, James Burke, Richard O’Brien, and Shih-Hsiu J. Wang. “Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation.” Acta Neuropathol Commun 10, no. 1 (March 3, 2022): 27. https://doi.org/10.1186/s40478-022-01330-x.
 
Harrison, William T., Jay B. Lusk, Beiyu Liu, John F. Ervin, Kim G. Johnson, Cynthia L. Green, and Shih-Hsiu J. Wang. “Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is independently associated with dementia and strongly associated with arteriolosclerosis in the oldest-old.” Acta Neuropathol 142, no. 5 (November 2021): 917–19. https://doi.org/10.1007/s00401-021-02360-w.