Understanding Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE): The Intersection of Pathology and Immune Dysregulation

Introduction

In the present state, a novel amnesic and AD-like dementia pathology emerges in the ageing brains, namely Limbic-predominant age-related TDP-43 encephalopathy (LATE). The disease is represented by aberrant splitting, clumping, phosphorylation, and massive accumulations of TDP-43 within the cytoplasm of cells involving neurons and glia. The abnormal regulation of TDP-43 is responsible for the mediated alteration of signaling events, such as deprived synaptic transmission, progressive neuronal degeneration, and motor deviations. Therefore, TDP-43 is a central player for LATE-associated CNS pathologies.

Material and Methods

Autopsy studies have revealed the characteristic misfolding of TDP-43 proteins in aged brains, illuminating the prevalence and distribution of TDP-43 in LATE. Additionally, recent research underscores the crucial role of impaired immune cells as key players in the neurodegeneration and the pathogenesis of TDP-43 proteinopathy. The systematic analysis of TDP-43 in LATE comprised 25 research findings with sample sizes ranging from 10 to 500 individuals.

Results

The objective of this review is to provide an extensive overview of the symptoms, neuropathological signs, proteinopathy, and approaches to diagnose LATE, with a focus on the way immune cell failure plays a role in its growth.

Discussion

This work aims to help comprehend LATE better by looking at how immune dysregulation and TDP-43 proteinopathy interact with each other. This will allow for new treatments that focus on immune pathways to help manage dementia.