Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology

Molecular Neurobiology
Sonia Do CarmoA C Cuello

Abstract

The cerebral accumulation and cytotoxicity of amyloid beta (Aβ) is central to Alzheimer's pathogenesis. However, little is known about how the amyloid pathology affects the global expression of brain proteins at different disease stages. In order to identify genotype and time-dependent significant changes in protein expression, we employed quantitative proteomics analysis of hippocampal tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology. McGill transgenic rats were compared to wild-type rats at early and late pathology stages, i.e., when intraneuronal Aβ amyloid burden is conspicuous and when extracellular amyloid plaques are abundant with more pronounced cognitive deficits. After correction for multiple testing, the expression levels of 64 proteins were found to be considerably different in transgenic versus wild-type rats at the pre-plaque stage (3 months), and 86 proteins in the post-plaque group (12 months), with only 9 differentially regulated proteins common to the 2 time-points. This minimal overlap supports the hypothesis that different molecular pathways are affected in the hippocampus at early and late stages of the amyloid pathology throughout its continuum. At early stages, disturbances ...Continue Reading

References

Aug 1, 1992·Circulation Research·F BennardiniM Chiesi
Jul 16, 1992·Nature·M B YaffeH Sternlicht
May 1, 1991·Neuron·E MasliahT Saitoh
Jan 1, 1990·Neurobiology of Aging·S W ScheffD A Price
Dec 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C W WongG G Glenner
Dec 6, 1985·Science·J W GeddesH C Chui
Apr 16, 1998·Biochimica Et Biophysica Acta·L E Rikans, K R Hornbrook
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·M P LambertW L Klein
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·A Y HsiaL Mucke
Mar 29, 2000·JAMA : the Journal of the American Medical Association·J NäslundJ D Buxbaum
Aug 29, 2000·Immunopharmacology·P Moseley
Nov 23, 2000·Journal of Neuropathology and Experimental Neurology·A NunomuraM A Smith
Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·K FassbenderT Hartmann
Aug 7, 2001·Journal of Neuropathology and Experimental Neurology·A NunomuraM A Smith
Feb 20, 2002·Biochemistry·Dominador J ManaloAlice Y-C Liu
Sep 25, 2002·Neurobiology of Disease·Elena TamagnoMassimo Tabaton
Oct 26, 2002·Science·Dennis J Selkoe
Oct 16, 2003·Trends in Biochemical Sciences·Jason C YoungF Ulrich Hartl
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Aug 5, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tara L SpiresBradley T Hyman
Aug 16, 2005·The Journal of Biological Chemistry·Youtao Song, Daniel C Masison

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Citations

Oct 27, 2018·Acta Neuropathologica·Lindsay A WelikovitchA Claudio Cuello
Oct 28, 2019·Proteomics·Alberto Valdés, Sara Bergström Lind
Jun 5, 2020·Quarterly Reviews of Biophysics·Tessa SinnigeMichele Vendruscolo
Oct 24, 2018·Journal of Alzheimer's Disease : JAD·Margaret M RyanJoanna M Williams
Mar 20, 2019·Frontiers in Pharmacology·A Claudio CuelloSonia Do Carmo

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Methods Mentioned

BETA
transgenic
ELISA
protein assay
Assay
ubiquitination
protein folding

Software Mentioned

- Pro Analyzer
Xcalibur
Ingenuity Pathway Analysis ( IPA
ImageJ
STRING
JMP ( SAS )
Protein Analysis Through Evolutionary Relationship ( PANTHER )
PMi Preview
Ingenuity Pathway Analysis ( IPA )
Fiji

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