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Intracellular Aβ pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study

Overview of attention for article published in Acta Neuropathologica Communications, June 2014
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Title
Intracellular Aβ pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study
Published in
Acta Neuropathologica Communications, June 2014
DOI 10.1186/2051-5960-2-61
Pubmed ID
Authors

M Florencia Iulita, Simon Allard, Luise Richter, Lisa-Marie Munter, Adriana Ducatenzeiler, Christoph Weise, Sonia Do Carmo, William L Klein, Gerhard Multhaup, A Claudio Cuello

Abstract

Numerous studies have implicated the abnormal accumulation of intraneuronal amyloid-beta (Abeta) as an important contributor to Alzheimer's disease (AD) pathology, capable of triggering neuroinflammation, tau hyperphosphorylation and cognitive deficits. However, the occurrence and pathological relevance of intracellular Abeta remain a matter of controversial debate. In this study, we have used a multidimensional approach including high-magnification and super-resolution microscopy, cerebro-spinal fluid (CSF) mass spectrometry analysis and ELISA to investigate the Abeta pathology and its associated cognitive impairments, in a novel transgenic rat model overexpressing human APP. Our microscopy studies with quantitative co-localization analysis revealed the presence of intraneuronal Abeta in transgenic rats, with an immunological signal that was clearly distinguished from that of the amyloid precursor protein (APP) and its C-terminal fragments (CTFs). The early intraneuronal pathology was accompanied by a significant elevation of soluble Abeta42 peptides that paralleled the presence and progression of early cognitive deficits, several months prior to amyloid plaque deposition. Abeta38, Abeta39, Abeta40 and Abeta42 peptides were detected in the rat CSF by MALDI-MS analysis even at the plaque-free stages; suggesting that a combination of intracellular and soluble extracellular Abeta may be responsible for impairing cognition at early time points. Taken together, our results demonstrate that the intraneuronal development of AD-like amyloid pathology includes a mixture of molecular species (Abeta, APP and CTFs) of which a considerable component is Abeta; and that the early presence of these species within neurons has deleterious effects in the CNS, even before the development of full-blown AD-like pathology.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 2 2%
Germany 1 1%
United Kingdom 1 1%
Switzerland 1 1%
Argentina 1 1%
Russia 1 1%
United States 1 1%
Unknown 75 90%

Demographic breakdown

Readers by professional status Count As %
Researcher 20 24%
Student > Ph. D. Student 19 23%
Student > Bachelor 13 16%
Student > Master 12 14%
Student > Doctoral Student 5 6%
Other 7 8%
Unknown 7 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 25%
Neuroscience 16 19%
Medicine and Dentistry 9 11%
Biochemistry, Genetics and Molecular Biology 7 8%
Psychology 5 6%
Other 12 14%
Unknown 13 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 June 2014.
All research outputs
#9,996,062
of 12,489,036 outputs
Outputs from Acta Neuropathologica Communications
#467
of 574 outputs
Outputs of similar age
#127,687
of 190,418 outputs
Outputs of similar age from Acta Neuropathologica Communications
#3
of 4 outputs
Altmetric has tracked 12,489,036 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 574 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
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