Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation
Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-06-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00139/full |
| _version_ | 1828813650148720640 |
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| author | Ditte Zerlang Christensen Melanie eHüttenrauch Miso eMitkovski Laurent ePradier Oliver eWirths |
| author_facet | Ditte Zerlang Christensen Melanie eHüttenrauch Miso eMitkovski Laurent ePradier Oliver eWirths |
| author_sort | Ditte Zerlang Christensen |
| collection | DOAJ |
| description | Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending on the mutant PS1 dosage, we demonstrate a clear aggravation in both plaque-associated and plaque-distant axonal degeneration, despite of an unchanged APP expression level. Amyloid-ß (Aβ) peptides were found to accumulate in axonal swellings as well as in axons and apical dendrites proximate to neurons accumulating intraneuronal Aβ in their cell bodies. This suggests that Aβ can be transported within neurites thereby contributing to axonal deficits. In addition, diffuse extracellular Aβ deposits were observed in the close vicinity of axonal spheroids accumulating intracellular Aβ, which might be indicative of a local Aβ release from sites of axonal damage. |
| first_indexed | 2024-12-12T10:05:47Z |
| format | Article |
| id | doaj.art-adea4d6f30f84e0eb5a25d79f58a70a1 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-12T10:05:47Z |
| publishDate | 2014-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-adea4d6f30f84e0eb5a25d79f58a70a12022-12-22T00:27:54ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652014-06-01610.3389/fnagi.2014.0013999854Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulationDitte Zerlang Christensen0Melanie eHüttenrauch1Miso eMitkovski2Laurent ePradier3Oliver eWirths4Department of Psychiatry, Göttingen UniversityDepartment of Psychiatry, Göttingen UniversityMax-Planck-Institute of Experimental MedicineSanofi-AventisDepartment of Psychiatry, Göttingen UniversityAbnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending on the mutant PS1 dosage, we demonstrate a clear aggravation in both plaque-associated and plaque-distant axonal degeneration, despite of an unchanged APP expression level. Amyloid-ß (Aβ) peptides were found to accumulate in axonal swellings as well as in axons and apical dendrites proximate to neurons accumulating intraneuronal Aβ in their cell bodies. This suggests that Aβ can be transported within neurites thereby contributing to axonal deficits. In addition, diffuse extracellular Aβ deposits were observed in the close vicinity of axonal spheroids accumulating intracellular Aβ, which might be indicative of a local Aβ release from sites of axonal damage.http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00139/fullAlzheimer DiseaseAmyloidAxonal TransportTransgenic miceintraneuronal amyloid-betaPresenilin |
| spellingShingle | Ditte Zerlang Christensen Melanie eHüttenrauch Miso eMitkovski Laurent ePradier Oliver eWirths Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation Frontiers in Aging Neuroscience Alzheimer Disease Amyloid Axonal Transport Transgenic mice intraneuronal amyloid-beta Presenilin |
| title | Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation |
| title_full | Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation |
| title_fullStr | Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation |
| title_full_unstemmed | Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation |
| title_short | Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aß accumulation |
| title_sort | axonal degeneration in an alzheimer mouse model is ps1 gene dose dependent and linked to intraneuronal a 223 accumulation |
| topic | Alzheimer Disease Amyloid Axonal Transport Transgenic mice intraneuronal amyloid-beta Presenilin |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00139/full |
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