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Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease

Janssen, L., Dubbelaar, M. L., Holtman, I. R., de Boer-Bergsma, J., Eggen, B. J. L., Boddeke, H. W. G. M., De Deyn, P. P. & Dam, van, D., Feb-2017, In : Biochimica et biophysica acta-Molecular basis of disease. 1863, 2, p. 395-405 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

Aging is the key risk factor for Alzheimer's disease (AD). In addition, the amyloid-beta (A beta) peptide is considered a critical neurotoxic agent in AD pathology. However, the connection between these factors is unclear. We aimed to provide an extensive characterization of the gene expression profiles of the amyloidosis APP23 model for AD and control mice and to evaluate the effect of aging on these profiles. We also correlated our findings to changes in soluble A beta-levels and other pathological and symptomatic features of the model. We observed a clear biphasic expression profile. The first phase displayed a maturation profile, which resembled features found in young carriers of familial AD mutations. The second phase reflected aging processes and showed similarities to the progression of human AD pathology. During this phase, the model displayed a clear upregulation of microglial activation and lysosomal pathways and downregulation of neuron differentiation and axon guidance pathways. Interestingly, the changes in expression were all correlated to aging in general, but appeared more extensive/accelerated in APP23 mice. (C) 2016 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalBiochimica et biophysica acta-Molecular basis of disease
Volume1863
Issue number2
Publication statusPublished - Feb-2017

    Keywords

  • Alzheimer's disease, Gene expression, RNA sequencing, Amyloid, APP23 mouse model, Inflammation, AMYLOID PRECURSOR PROTEIN, DENDRITIC SPINE MORPHOGENESIS, GENE-EXPRESSION DATA, TRANSGENIC MICE, BETA-PROTEIN, SYNAPTIC PLASTICITY, SWEDISH MUTATION, CATHEPSIN-B, ACTIN CYTOSKELETON, MISSENSE MUTATIONS

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