4.5 Article

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

期刊

NEUROIMAGE-CLINICAL
卷 34, 期 -, 页码 -

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.nicl.2022.102954

关键词

Alzheimer's disease; TDP-43; MRI; LATE; Old age FTLD

资金

  1. US National Institutes of Health (NIH) [R01 AG037491-11, RF1 NS120992, P30 AG062677, U01 AG006786, R35 AG11378, R01 AG041851]

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The study found differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43, with faster atrophy rates in certain brain regions for FTLD-TDP and faster hippocampal atrophy rates in AD-TDP type-a.
Transactive response DNA-binding protein of similar to 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- a and neurofibrillary tangle-associated type-beta. 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 similar to 10 years, we used a Bayesian hierarchical linear model to quantify similarities and differences between the non-FTLD TDP-43 (type-alpha/type-beta) 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 alpha/beta based on presence/absence of intermediate-high likelihood AD: AD-TDP type-beta (n = 90), AD-TDP type- a (n = 104), and Pure-TDP (n = 31, all type-alpha). 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 fastest rates. Older FTLD-TDP showed a limbic predominant pattern of neurodegeneration. AD-TDP type- a showed faster rates of hippocampal atrophy and smaller volumes of amygdala, temporal pole, and inferior temporal lobe compared to AD-TDP type-beta. Pure-TDP was associated with slowest rates and less atrophy in all brain regions. The results suggest that there are differences and similarities in longitudinal brain volume loss between FTLD-TDP and non-FTLD TDP-43. Within FTLD-TDP age plays a role in which brain regions are the most affected. Additionally, brain atrophy regional rates also vary by non-FTLD TDP-43 type.

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