Please use this identifier to cite or link to this item: https://doi.org/10.1186/2051-5960-2-61
Title: Intracellular A? pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: A multidimensional study
Authors: Iulita, M.F
Allard, S
Richter, L
Munter, L.M
Ducatenzeiler, A
Weise, C
DoCarmo, S
Klein, W.L
Multhaup, G
Cuello, A.C 
Keywords: amyloid beta protein
amyloid beta protein[1-40]
amyloid beta-protein (1-42)
amyloid precursor protein
peptide fragment
secretase
animal
auditory stimulation
brain
cerebrospinal fluid
cognitive defect
conditioning
disease model
fear
gene expression regulation
genetics
human
intracellular fluid
metabolism
mutation
pain measurement
pathology
physiology
rat
recognition
regression analysis
transgenic rat
adverse effects
Acoustic Stimulation
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Amyloid Precursor Protein Secretases
Animals
Brain
Cognition Disorders
Conditioning (Psychology)
Disease Models, Animal
Fear
Gene Expression Regulation
Humans
Intracellular Fluid
Mutation
Pain Measurement
Peptide Fragments
Rats
Rats, Transgenic
Recognition (Psychology)
Regression Analysis
Issue Date: 2014
Citation: Iulita, M.F, Allard, S, Richter, L, Munter, L.M, Ducatenzeiler, A, Weise, C, DoCarmo, S, Klein, W.L, Multhaup, G, Cuello, A.C (2014). Intracellular A? pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: A multidimensional study. Acta Neuropathologica Communications 2 (1) : 61. ScholarBank@NUS Repository. https://doi.org/10.1186/2051-5960-2-61
Rights: Attribution 4.0 International
Abstract: Numerous studies have implicated the abnormal accumulation of intraneuronal amyloid-? (A?) 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 A? 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 A? 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 A? 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 A?42 peptides that paralleled the presence and progression of early cognitive deficits, several months prior to amyloid plaque deposition. A?38, A?39, A?40 and A?42 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 A? 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 (A?, APP and CTFs) of which a considerable component is A?; 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. © 2014 Iulita et al.; licensee BioMed Central Ltd.
Source Title: Acta Neuropathologica Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/182028
ISSN: 20515960
DOI: 10.1186/2051-5960-2-61
Rights: Attribution 4.0 International
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