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Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease.

Abstract

In the present report, we extend previous findings in the 5XFAD mouse model and demonstrate that these mice develop an age-dependent motor phenotype in addition to working memory deficits and reduced anxiety levels as demonstrated in an elevated plus maze task. Employing a variety of N- and C-terminal specific Aβ antibodies, abundant intraneuronal and plaque-associated pathology, including accumulation of pyroglutamate Aβ, was observed as early as the age of 3 months. Using unbiased stereology, we demonstrate that the 5XFAD mice develop a significant selective neuron loss in layer 5 of the cortex, leaving the overall neuron number of the total frontal cortex and hippocampus unaffected. This observation coincides with the accumulation of intraneuronal Aβ peptides only in cortical Layer 5, but not in CA1, despite comparable APP expression levels. The motor phenotype correlates with abundant spinal cord pathology, as demonstrated by abundant intraneuronal Aβ accumulation and extracellular plaque deposition. In addition, comparable to the APP/PS1KI mouse model, 5XFAD mice develop an age-dependent axonopathy likely contributing to the behavioral deficits.

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  • Authors+Show Affiliations

    ,

    Division of Molecular Psychiatry, Alzheimer Ph.D., Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-str. 5, 37075 Goettingen, Germany.

    , , ,

    Source

    Neurobiology of aging 33:1 2012 Jan pg 196.e29-40

    MeSH

    Aging
    Alzheimer Disease
    Amyloid beta-Peptides
    Animals
    Anxiety
    Axons
    Central Nervous System
    Disease Models, Animal
    Male
    Memory, Short-Term
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Nerve Degeneration
    Neurons
    Plaque, Amyloid
    Psychomotor Performance

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20619937

    Citation

    Jawhar, Sadim, et al. "Motor Deficits, Neuron Loss, and Reduced Anxiety Coinciding With Axonal Degeneration and Intraneuronal Aβ Aggregation in the 5XFAD Mouse Model of Alzheimer's Disease." Neurobiology of Aging, vol. 33, no. 1, 2012, pp. 196.e29-40.
    Jawhar S, Trawicka A, Jenneckens C, et al. Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging. 2012;33(1):196.e29-40.
    Jawhar, S., Trawicka, A., Jenneckens, C., Bayer, T. A., & Wirths, O. (2012). Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease. Neurobiology of Aging, 33(1), pp. 196.e29-40. doi:10.1016/j.neurobiolaging.2010.05.027.
    Jawhar S, et al. Motor Deficits, Neuron Loss, and Reduced Anxiety Coinciding With Axonal Degeneration and Intraneuronal Aβ Aggregation in the 5XFAD Mouse Model of Alzheimer's Disease. Neurobiol Aging. 2012;33(1):196.e29-40. PubMed PMID: 20619937.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Aβ aggregation in the 5XFAD mouse model of Alzheimer's disease. AU - Jawhar,Sadim, AU - Trawicka,Anna, AU - Jenneckens,Carolin, AU - Bayer,Thomas A, AU - Wirths,Oliver, Y1 - 2010/07/09/ PY - 2010/01/12/received PY - 2010/05/10/revised PY - 2010/05/14/accepted PY - 2010/7/13/entrez PY - 2010/7/14/pubmed PY - 2012/3/14/medline SP - 196.e29 EP - 40 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 33 IS - 1 N2 - In the present report, we extend previous findings in the 5XFAD mouse model and demonstrate that these mice develop an age-dependent motor phenotype in addition to working memory deficits and reduced anxiety levels as demonstrated in an elevated plus maze task. Employing a variety of N- and C-terminal specific Aβ antibodies, abundant intraneuronal and plaque-associated pathology, including accumulation of pyroglutamate Aβ, was observed as early as the age of 3 months. Using unbiased stereology, we demonstrate that the 5XFAD mice develop a significant selective neuron loss in layer 5 of the cortex, leaving the overall neuron number of the total frontal cortex and hippocampus unaffected. This observation coincides with the accumulation of intraneuronal Aβ peptides only in cortical Layer 5, but not in CA1, despite comparable APP expression levels. The motor phenotype correlates with abundant spinal cord pathology, as demonstrated by abundant intraneuronal Aβ accumulation and extracellular plaque deposition. In addition, comparable to the APP/PS1KI mouse model, 5XFAD mice develop an age-dependent axonopathy likely contributing to the behavioral deficits. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/20619937/Motor_deficits_neuron_loss_and_reduced_anxiety_coinciding_with_axonal_degeneration_and_intraneuronal_Aβ_aggregation_in_the_5XFAD_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(10)00241-1 DB - PRIME DP - Unbound Medicine ER -