Macroscopic Localized Subicular Thinning as a Potential Indicator of Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 79 (3-4) ◽  
pp. 200-205 ◽  
Author(s):  
Hiroki Yamada ◽  
Takahiro Takeda ◽  
Toshiki Uchihara ◽  
Shizuko Sato ◽  
Susumu Kirimura ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nucleus Accumbens ◽  
Dna Binding ◽  
Alzheimer Disease ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Potential Indicator ◽  
Transentorhinal Cortex ◽  
Als Patients ◽  
Lateral Sclerosis

Subicular degeneration occurs in amyotrophic lateral sclerosis (ALS) patients. However, it was unknown whether microscopic subicular degeneration could be observed as macroscopic changes and whether these changes were associated with the transactive-response DNA binding protein 43 kDa (TDP-43) pathology. Topographic differences between subicular degeneration caused by ALS and Alzheimer disease (AD) had also not been characterized. Here we investigated the subiculum and related areas in autopsied brains from 3 ALS and 3 AD patients. Macroscopic subicular thinning and corresponding astrocytosis were pronounced in ALS compared to AD. This thinning was frequently accompanied by TDP-43 pathology in the transentorhinal cortex and nucleus accumbens. The preferential susceptibility of the perforant pathway to TDP-43 deposition may be an underlying cause of subicular thinning in ALS.

Cerebrospinal Fluid TAR DNA-Binding Protein 43 Combined with Tau Proteins as a Candidate Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Spectrum Disorders

2017 ◽  
Vol 44 (3-4) ◽  
pp. 144-152 ◽  
Author(s):  
Mara Bourbouli ◽  
Michael Rentzos ◽  
Anastasia Bougea ◽  
Vasiliki Zouvelou ◽  
Vasilios C. Constantinides ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Dna Binding ◽  
Frontotemporal Dementia ◽  
Tau Protein ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Amyloid Peptide ◽  
Spectrum Disorders ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are nowadays recognized as spectrum disorders with a molecular link, the TAR DNA-binding protein 43 (TDP-43), rendering it a surrogate biomarker for these disorders. Methods: We measured cerebrospinal fluid (CSF) levels of TDP-43, beta-amyloid peptide with 42 amino acids (Aβ42), total tau protein (τT), and tau protein phosphorylated at threonine 181 (τP-181) in 32 patients with ALS, 51 patients with FTD, and 17 healthy controls. Double-sandwich commercial enzyme-linked immunosorbent assays were used for measurements. Results: Both ALS and FTD patients presented with higher TDP-43 and τT levels compared to the control group. The combination of biomarkers in the form of the TDP-43 × τT / τP-181 formula achieved the best discrimination between ALS or FTD and controls, with sensitivities and specificities >0.8. Conclusion: Combined analysis of TDP-43, τT, and τP-181 in CSF may be useful for the antemortem diagnosis of ALS and FTD.

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