Abstract
Background TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as “Lin bodies,” located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for astrocytes, IBA1 for microglia) and ferritin. Analyses were conducted on post-mortem brain tissues collected from individuals with pathologically confirmed Alzheimer’s disease neuropathological changes (ADNC) and LATE-NC.
Results As shown previously, there was a robust association between Lin bodies and GFAP-positive astrocyte processes. Moreover, we also observed Lin bodies frequently co-localizing with ferritin, suggesting a potential link to compromised vascular integrity. Subsequent analyses demonstrated increased astrocytosis near Lin body- positive vessels compared to those without Lin bodies, particularly in ADNC cases. These results suggest that the accumulation of Lin bodies may elicit an increased glial response, particularly among astrocytes, possibly related to impaired vascular integrity.
Conclusions Lin bodies are associated with a local reactive glial response. The strong association of Lin bodies with ferritin suggests that the loss of vascular integrity may be either a cause or a consequence of the pTDP-43 pathology. The reactive glia surrounding the affected vessels could further compromise vascular function.
Document Type
Article
Publication Date
7-2024
Digital Object Identifier (DOI)
https://doi.org/10.1186/s40478-024-01826-8
Funding Information
National Institutes of Health supported research reported in this publication under award numbers T32 AG078110, R21 AG066865, R01 NS103785, R01 NS120882, R01 AG068215, RF1 NS119165, R01 AG061111, R01 AG057187, P30 AG072946, RF1 NS118584, and P01 AG078116.
Repository Citation
Shahidehpour, Ryan K.; Nelson, Peter T.; and Bachstetter, Adam D., "A pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC" (2024). Neurology Faculty Publications. 129.
https://uknowledge.uky.edu/neurology_facpub/129
Notes/Citation Information
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