Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases
Background: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND).Objective: Considering that dementia is one of the most frequently non-motor symptoms in ALS and that hippocampus is one of the brain areas with greater...
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Frontiers Media S.A.
2016-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00195/full |
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| author | Ulises Gomez-Pinedo Rocio Nur Villar-Quiles Lucia Galan Jordi A. Matias-Guiu Maria Soledad Benito-Martin Antonio Guerrero-Sola Teresa Moreno-Ramos Jorge Matias-Guiu |
| author_facet | Ulises Gomez-Pinedo Rocio Nur Villar-Quiles Lucia Galan Jordi A. Matias-Guiu Maria Soledad Benito-Martin Antonio Guerrero-Sola Teresa Moreno-Ramos Jorge Matias-Guiu |
| author_sort | Ulises Gomez-Pinedo |
| collection | DOAJ |
| description | Background: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND).Objective: Considering that dementia is one of the most frequently non-motor symptoms in ALS and that hippocampus is one of the brain areas with greater presence of amyloid related changes in neurodegenerative diseases, our aim was to analyse the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-FTD.Methods: We included 9 patients with MND and 4 controls. Immunohistochemical studies and confocal microscopy were used to analyse the expression of APP, TDP-43, pho-TDP-43, Aβ, AICD peptide, Fe65 protein, and pho-TAU in the hippocampus of 7 patients with ALS, 2 patients with ALS-FTD, and 4 controls. These findings were correlated with clinical data.Results: Patients displayed increased expression of APP and Aβ peptide. The latter was correlated with cytoplasmic pho-TDP-43 expression. We also found decreased Fe65 expression. A parallel increase in AICD expression was not found. Patients showed increased expression of pho-TAU in the hippocampus. Findings were similar in patients with ALS and those with ALS-FTD, though more marked in the latter group.Conclusion: Post-mortem analyses showed that the amyloid cascade is activated in the hippocampus of patients with MND and correlated with cytoplasmic pho-TDP-43 expression. The number of intra- or extracellular aggregates of Aβ peptides was not significant. |
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| language | English |
| last_indexed | 2024-12-23T21:17:00Z |
| publishDate | 2016-11-01 |
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| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-a23a8eaf705c4210bedaaf92339bafc92022-12-21T17:30:52ZengFrontiers Media S.A.Frontiers in Neurology1664-22952016-11-01710.3389/fneur.2016.00195221808Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseasesUlises Gomez-Pinedo0Rocio Nur Villar-Quiles1Lucia Galan2Jordi A. Matias-Guiu3Maria Soledad Benito-Martin4Antonio Guerrero-Sola5Teresa Moreno-Ramos6Jorge Matias-Guiu7Hospital Clinico San Carlos, IdISSCHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainHospital Clinico San Carlos, IdISSCHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainHospital Clínico San Carlos, IdISSC, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, SpainBackground: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND).Objective: Considering that dementia is one of the most frequently non-motor symptoms in ALS and that hippocampus is one of the brain areas with greater presence of amyloid related changes in neurodegenerative diseases, our aim was to analyse the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-FTD.Methods: We included 9 patients with MND and 4 controls. Immunohistochemical studies and confocal microscopy were used to analyse the expression of APP, TDP-43, pho-TDP-43, Aβ, AICD peptide, Fe65 protein, and pho-TAU in the hippocampus of 7 patients with ALS, 2 patients with ALS-FTD, and 4 controls. These findings were correlated with clinical data.Results: Patients displayed increased expression of APP and Aβ peptide. The latter was correlated with cytoplasmic pho-TDP-43 expression. We also found decreased Fe65 expression. A parallel increase in AICD expression was not found. Patients showed increased expression of pho-TAU in the hippocampus. Findings were similar in patients with ALS and those with ALS-FTD, though more marked in the latter group.Conclusion: Post-mortem analyses showed that the amyloid cascade is activated in the hippocampus of patients with MND and correlated with cytoplasmic pho-TDP-43 expression. The number of intra- or extracellular aggregates of Aβ peptides was not significant.http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00195/fullAmyotrophic Lateral SclerosisFrontotemporal Dementiaamyloid precursor proteintau proteinTDP-43Aβ peptide |
| spellingShingle | Ulises Gomez-Pinedo Rocio Nur Villar-Quiles Lucia Galan Jordi A. Matias-Guiu Maria Soledad Benito-Martin Antonio Guerrero-Sola Teresa Moreno-Ramos Jorge Matias-Guiu Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases Frontiers in Neurology Amyotrophic Lateral Sclerosis Frontotemporal Dementia amyloid precursor protein tau protein TDP-43 Aβ peptide |
| title | Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| title_full | Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| title_fullStr | Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| title_full_unstemmed | Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| title_short | Immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| title_sort | immununochemical markers of the amyloid cascade in the hippocampus in motor neuron diseases |
| topic | Amyotrophic Lateral Sclerosis Frontotemporal Dementia amyloid precursor protein tau protein TDP-43 Aβ peptide |
| url | http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00195/full |
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