White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis
<p><strong>OBJECTIVE:</strong> The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or dep...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2019
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| _version_ | 1797069370558513152 |
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| author | Mollink, J Hiemstra, M Miller, K Huszar, I Jenkinson, M Raaphorst, J Wiesmann, M Ansorge, O Pallebage-Gamarallage, M Van Cappellen Van Walsum, A |
| author_facet | Mollink, J Hiemstra, M Miller, K Huszar, I Jenkinson, M Raaphorst, J Wiesmann, M Ansorge, O Pallebage-Gamarallage, M Van Cappellen Van Walsum, A |
| author_sort | Mollink, J |
| collection | OXFORD |
| description | <p><strong>OBJECTIVE:</strong> The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells.</p> <p><strong>METHODS:</strong> We used diffusion Magnetic Resonance Imaging (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post mortem hippocampus specimens from controls (n = 5) and ALS patients (n = 14) to study white matter degeneration in the perforant path.</p> <p><strong>RESULTS:</strong> diffusion Magnetic Resonance Imaging demonstrated a decrease in fractional anisotropy (P = 0.01) and an increase in mean diffusivity (P = 0.01) in the perforant path in ALS compared to controls. PLI-myelin density was lower in ALS (P = 0.05) and correlated with fractional anisotropy (r = 0.52, P = 0.03). These results were confirmed by immunohistochemistry; both myelin (proteolipid protein, P = 0.03) and neurofilaments (SMI-312, P = 0.02) were lower in ALS. Two out of the fourteen ALS cases showed pTDP-43 pathology in the dentate gyrus, but with comparable myelination levels in the perforant path to other ALS cases.</p> <p><strong>CONCLUSION:</strong> We conclude that degeneration of the perforant path occurs in ALS patients and that this may occur before, or independent of, pTDP-43 aggregation in the dentate gyrus of the hippocampus. Future research should focus on correlating the degree of cognitive decline to the amount of white matter atrophy in the perforant path.</p> |
| first_indexed | 2024-03-06T22:23:26Z |
| format | Journal article |
| id | oxford-uuid:55d578ac-8c1b-4c7e-bc4e-61094fd05087 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:23:26Z |
| publishDate | 2019 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:55d578ac-8c1b-4c7e-bc4e-61094fd050872022-03-26T16:46:44ZWhite matter changes in the perforant path area in patients with amyotrophic lateral sclerosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:55d578ac-8c1b-4c7e-bc4e-61094fd05087EnglishSymplectic Elements at OxfordWiley2019Mollink, JHiemstra, MMiller, KHuszar, IJenkinson, MRaaphorst, JWiesmann, MAnsorge, OPallebage-Gamarallage, M Van Cappellen Van Walsum, A<p><strong>OBJECTIVE:</strong> The aim of this study was to test the hypothesis that white matter degeneration of the perforant path - as part of the Papez circuit - is a key feature of amyotrophic lateral sclerosis (ALS), even in the absence of frontotemporal dementia (FTD) or deposition of pTDP-43 inclusions in hippocampal granule cells.</p> <p><strong>METHODS:</strong> We used diffusion Magnetic Resonance Imaging (dMRI), polarized light imaging (PLI) and immunohistochemical analysis of post mortem hippocampus specimens from controls (n = 5) and ALS patients (n = 14) to study white matter degeneration in the perforant path.</p> <p><strong>RESULTS:</strong> diffusion Magnetic Resonance Imaging demonstrated a decrease in fractional anisotropy (P = 0.01) and an increase in mean diffusivity (P = 0.01) in the perforant path in ALS compared to controls. PLI-myelin density was lower in ALS (P = 0.05) and correlated with fractional anisotropy (r = 0.52, P = 0.03). These results were confirmed by immunohistochemistry; both myelin (proteolipid protein, P = 0.03) and neurofilaments (SMI-312, P = 0.02) were lower in ALS. Two out of the fourteen ALS cases showed pTDP-43 pathology in the dentate gyrus, but with comparable myelination levels in the perforant path to other ALS cases.</p> <p><strong>CONCLUSION:</strong> We conclude that degeneration of the perforant path occurs in ALS patients and that this may occur before, or independent of, pTDP-43 aggregation in the dentate gyrus of the hippocampus. Future research should focus on correlating the degree of cognitive decline to the amount of white matter atrophy in the perforant path.</p> |
| spellingShingle | Mollink, J Hiemstra, M Miller, K Huszar, I Jenkinson, M Raaphorst, J Wiesmann, M Ansorge, O Pallebage-Gamarallage, M Van Cappellen Van Walsum, A White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title | White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title_full | White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title_fullStr | White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title_full_unstemmed | White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title_short | White matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
| title_sort | white matter changes in the perforant path area in patients with amyotrophic lateral sclerosis |
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