Patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share clinical overlap in terms of cognitive decline and are both characterised by the deposition of pathological TDP-43 inclusions in the brain. Here, we hypothesize that white matter degeneration of the perforant path in the hippocampus is a key feature of ALS patients developing FTD-like symptoms. Using diffusion MRI, polarized light imaging (PLI) and immunohistochemical (IHC) analysis we analysed white matter in the perforant path. dMRI and PLI measures suggest white matter degeneration in this pathway; however, densitometric analysis of IHC did not support this interpretation.
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