Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment

Genes, Brain, and Behavior
T A Bayer, O Wirths

Abstract

Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.

References

Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Oct 1, 1991·Trends in Pharmacological Sciences·J Hardy, D Allsop
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Oct 23, 1997·Science·J H Morrison, P R Hof
Oct 31, 1998·Nature·M E CalhounM Jucker
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·A Y HsiaL Mucke
May 15, 2002·Dementia and Geriatric Cognitive Disorders·Anna F PetterssonLars-Olof Wahlund
Nov 5, 2002·The American Journal of Pathology·Reisuke H TakahashiGunnar K Gouras
May 14, 2003·Neurobiology of Disease·Alena V SavonenkoAlicja L Markowska
Nov 1, 1958·Psychological Bulletin·W N DEMBER, H FOWLER
Nov 26, 2003·Experimental Neurology·Véronique BlanchardLaurent Pradier
Dec 4, 2003·Neurobiology of Aging·Salvatore OddoFrank M LaFerla
Mar 25, 2004·The American Journal of Pathology·Christoph SchmitzThomas A Bayer
Oct 29, 2004·The American Journal of Pathology·Dominique LanguiCharles Duyckaerts
Feb 26, 2005·Science·Gorazd B StokinLawrence S B Goldstein
Mar 5, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Orly LazarovSangram S Sisodia
May 25, 2005·Neurology·N ScarmeasY Stern
Jun 28, 2005·Neurobiology of Aging·Mark A LovellWilliam R Markesbery
Jul 5, 2005·Neurobiology of Aging·Michael EwersDiana S Woodruff-Pak
Aug 17, 2005·The Journal of Biological Chemistry·Alessandra PicciniMassimo Tabaton
Oct 15, 2005·Nature Reviews. Neuroscience·Michael Coleman
Mar 8, 2006·Acta Neuropathologica·Oliver WirthsThomas A Bayer

❮ Previous
Next ❯

Citations

Mar 17, 2011·Brain Structure & Function·Marijke A M LemmensChristoph Schmitz
Jul 28, 2012·International Journal of Molecular Sciences·Li Na ZhaoLock Yue Chew
Jun 12, 2016·Molecular Neurodegeneration·Claire S Harwell, Michael P Coleman
Mar 10, 2012·Life Sciences·Oliver Wirths, Thomas A Bayer
Dec 21, 2011·Journal of Neuroscience Research·Kimihiko SatoShoichi Ishiura
Apr 24, 2010·Journal of Neurochemistry·Ioannis DafnisAngeliki Chroni
Jul 3, 2020·Nature Reviews. Drug Discovery·Kimberly Scearce-LevieJoseph W Lewcock
Dec 8, 2015·Journal of Alzheimer's Disease : JAD·Robert WeissmannOliver Wirths
May 16, 2019·The Journal of Physiological Sciences : JPS·Dafeng BaiYan Cui
Sep 6, 2008·Neurobiology of Aging·Reisuke H TakahashiGunnar K Gouras

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.