TDP-43-associated atrophy in brains with and without frontotemporal lobar degeneration

作者：Marina Buciuc, Peter R. Martin, Nirubol Tosakulwong, Melissa E. Murray, Leonard Petrucelli, Matthew L. Senjem, Anthony J. Spychalla, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Joseph E. Parisi, R. Ross Reichard, Dennis W. Dickson, Clifford R. Jack, Jennifer L. Whitwell, Keith A. Josephs · 发表于：NeuroImage Clinical · 年份：2022 · DOI：10.1016/j.nicl.2022.102954 · 被引用次数：16 · 研究领域：Amyotrophic Lateral Sclerosis Research、Alzheimer's disease research and treatments、Parkinson's Disease Mechanisms and Treatments

Transactive response DNA-binding protein of ∼43 kDa (TDP-43), a primary pathologic substrate in tau-negative frontotemporal lobar degeneration (FTLD), is also often found in the brains of elderly individuals without FTLD and is a key player in the process of neurodegeneration in brains with and without FTLD. It is unknown how rates and trajectories of TDP-43-associated brain atrophy compare between these two groups. Additionally, non-FTLD TDP-43 inclusions are not homogeneous and can be divided into two morphologic types: type-α and neurofibrillary tangle-associated type-β. Therefore, we explored whether neurodegeneration also varies due to the morphologic type. In this longitudinal retrospective study of 293 patients with 843 MRI scans spanning over ∼10 years, we used a Bayesian hierarchical linear model to quantify similarities and differences between the non-FTLD TDP-43 (type-α/type-β) and FTLD-TDP (n = 68) in both regional volume at various timepoints before death and annualized rate of atrophy. Since Alzheimer's disease (AD) is a frequent co-pathology in non-FTLD TDP-43, we further divided types α/β based on presence/absence of intermediate-high likelihood AD: AD-TDP type-β (n = 90), AD-TDP type-α (n = 104), and Pure-TDP (n = 31, all type-α). FTLD-TDP was associated with faster atrophy rates in the inferior temporal lobe and temporal pole compared to all non-FTLD TDP-43 groups. The atrophy rate in the frontal lobe was modulated by age with younger FTLD-TDP having the fas...