Matches in SemOpenAlex for { <https://semopenalex.org/work/W2911830075> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2911830075 abstract "Despite the development of many transgenic mouse lines with abundant β–amyloid plaques, the link between amyloid plaques and neuron loss has not been established. Recent evidence points to an important role of intraneuronal Aβ aggregation in this process. N–modification and truncation of Aβ peptides seem to confer resistance against degradation, thereby increasing cytotoxicity due to a higher potential to oligomerize. We investigated bigenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and knocked–in human mutant presenilin–1 (M233T/L235P), named APP751/PS1KI. The objective was to study intraneuronal pathology and consequences of neuron loss. mRNA profiling, neuropathology of brain and spinal cord, 2D gel electrophoresis, stereology. Substantial neuron loss was found in the hippocampal pyramidal CA1/2 layer at six months (∼20%), and at 10 months of age (∼50%). The loss of neurons did not correlate with plaque load. Most remarkable, using 2D–gel electrophoresis, the mice exhibited a heterogeneous variety of N–truncated and modified Aβ42 peptides. Before plaque formation, we could detect intraneuronal oligomeric Aβ accumulation and peptides beginning with aspartate at position 1 (L– and D), and glutamate at position 3 (pyro–Glu), the latter has been shown to be the most prominent species in sporadic AD brains. Interestingly, using Chip–based mRNA profiling and qRT–PCR verification, we identified several mRNAs involved in iron/copper homeostasis, which were up–regulated in an age–dependent manner. In the spinal cord, signs for Wallerian degeneration and axonal transport problems in an age dependent manner were observed. Overall, the mouse model shows major AD–typical neuropathological hallmarks with abundant neuron loss that is clearly independent from extracellular amyloid deposition and identifies intraneuronal Aβ X–42 as a major neurotoxic risk factor. Moreover, pathological signs, like demyelination, gliosis and deteriorated axon tracts, markers for axonal degeneration are found independent from extracellular Aβ depositions. We suggest a modified amyloid hypothesis with intracellular aggregation as the major toxic factor, which induces axonal mistrafficking, and neurodegeneration. N–truncated and modified Aβ peptides are of particular importance, because they are more stable and are therefore at higher risk for intraneuronal aggregation." @default.
- W2911830075 created "2019-02-21" @default.
- W2911830075 creator A5000431138 @default.
- W2911830075 creator A5019084646 @default.
- W2911830075 creator A5019205615 @default.
- W2911830075 creator A5019892853 @default.
- W2911830075 creator A5023317571 @default.
- W2911830075 creator A5028054357 @default.
- W2911830075 creator A5034130805 @default.
- W2911830075 creator A5037528046 @default.
- W2911830075 creator A5060970793 @default.
- W2911830075 creator A5062788542 @default.
- W2911830075 date "2006-07-01" @default.
- W2911830075 modified "2023-10-16" @default.
- W2911830075 title "O2-04-06: New lessons form the APP/PS1 transgenic mouse model with neuron loss: Metal biology, axonal degeneration and intraneuronal N-modified Aβ aggregation" @default.
- W2911830075 doi "https://doi.org/10.1016/j.jalz.2006.05.134" @default.
- W2911830075 hasPublicationYear "2006" @default.
- W2911830075 type Work @default.
- W2911830075 sameAs 2911830075 @default.
- W2911830075 citedByCount "0" @default.
- W2911830075 crossrefType "journal-article" @default.
- W2911830075 hasAuthorship W2911830075A5000431138 @default.
- W2911830075 hasAuthorship W2911830075A5019084646 @default.
- W2911830075 hasAuthorship W2911830075A5019205615 @default.
- W2911830075 hasAuthorship W2911830075A5019892853 @default.
- W2911830075 hasAuthorship W2911830075A5023317571 @default.
- W2911830075 hasAuthorship W2911830075A5028054357 @default.
- W2911830075 hasAuthorship W2911830075A5034130805 @default.
- W2911830075 hasAuthorship W2911830075A5037528046 @default.
- W2911830075 hasAuthorship W2911830075A5060970793 @default.
- W2911830075 hasAuthorship W2911830075A5062788542 @default.
- W2911830075 hasConcept C102230213 @default.
- W2911830075 hasConcept C104317684 @default.
- W2911830075 hasConcept C141035611 @default.
- W2911830075 hasConcept C142724271 @default.
- W2911830075 hasConcept C143065580 @default.
- W2911830075 hasConcept C148762608 @default.
- W2911830075 hasConcept C153911025 @default.
- W2911830075 hasConcept C169760540 @default.
- W2911830075 hasConcept C175344181 @default.
- W2911830075 hasConcept C185592680 @default.
- W2911830075 hasConcept C2778794669 @default.
- W2911830075 hasConcept C2779134260 @default.
- W2911830075 hasConcept C2780775167 @default.
- W2911830075 hasConcept C31705614 @default.
- W2911830075 hasConcept C502032728 @default.
- W2911830075 hasConcept C55493867 @default.
- W2911830075 hasConcept C71924100 @default.
- W2911830075 hasConcept C86803240 @default.
- W2911830075 hasConcept C95444343 @default.
- W2911830075 hasConceptScore W2911830075C102230213 @default.
- W2911830075 hasConceptScore W2911830075C104317684 @default.
- W2911830075 hasConceptScore W2911830075C141035611 @default.
- W2911830075 hasConceptScore W2911830075C142724271 @default.
- W2911830075 hasConceptScore W2911830075C143065580 @default.
- W2911830075 hasConceptScore W2911830075C148762608 @default.
- W2911830075 hasConceptScore W2911830075C153911025 @default.
- W2911830075 hasConceptScore W2911830075C169760540 @default.
- W2911830075 hasConceptScore W2911830075C175344181 @default.
- W2911830075 hasConceptScore W2911830075C185592680 @default.
- W2911830075 hasConceptScore W2911830075C2778794669 @default.
- W2911830075 hasConceptScore W2911830075C2779134260 @default.
- W2911830075 hasConceptScore W2911830075C2780775167 @default.
- W2911830075 hasConceptScore W2911830075C31705614 @default.
- W2911830075 hasConceptScore W2911830075C502032728 @default.
- W2911830075 hasConceptScore W2911830075C55493867 @default.
- W2911830075 hasConceptScore W2911830075C71924100 @default.
- W2911830075 hasConceptScore W2911830075C86803240 @default.
- W2911830075 hasConceptScore W2911830075C95444343 @default.
- W2911830075 hasIssue "3S_Part_2" @default.
- W2911830075 hasLocation W29118300751 @default.
- W2911830075 hasOpenAccess W2911830075 @default.
- W2911830075 hasPrimaryLocation W29118300751 @default.
- W2911830075 hasRelatedWork W1996664269 @default.
- W2911830075 hasRelatedWork W2005899728 @default.
- W2911830075 hasRelatedWork W2013205211 @default.
- W2911830075 hasRelatedWork W2063310725 @default.
- W2911830075 hasRelatedWork W2077464099 @default.
- W2911830075 hasRelatedWork W2082412775 @default.
- W2911830075 hasRelatedWork W2084499843 @default.
- W2911830075 hasRelatedWork W2092512185 @default.
- W2911830075 hasRelatedWork W2101556341 @default.
- W2911830075 hasRelatedWork W2471923151 @default.
- W2911830075 hasVolume "2" @default.
- W2911830075 isParatext "false" @default.
- W2911830075 isRetracted "false" @default.
- W2911830075 magId "2911830075" @default.
- W2911830075 workType "article" @default.