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

Leen Janssen; Marissa L. Dubbelaar; Inge R. Holtman; Jelkje de Boer-Bergsma; Bart J. L. Eggen; Hendrikus W. G. M. Boddeke; Peter P. De Deyn; Debby Dam, van

doi:10.1016/j.bbadis.2016.11.014

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

Leen Janssen, Marissa L. Dubbelaar, Inge R. Holtman, Jelkje de Boer-Bergsma, Bart J. L. Eggen, Hendrikus W. G. M. Boddeke, Peter P. De Deyn, Debby Dam, van

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 language	English
Pages (from-to)	395-405
Number of pages	11
Journal	Biochimica et biophysica acta-Molecular basis of disease
Volume	1863
Issue number	2
DOIs	https://doi.org/10.1016/j.bbadis.2016.11.014
Publication status	Published - 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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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. (2017). Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease. Biochimica et biophysica acta-Molecular basis of disease, 1863(2), 395-405. https://doi.org/10.1016/j.bbadis.2016.11.014

@article{015d2377443d4cf8891bda031161863f,

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

abstract = "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.",

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",

author = "Leen Janssen and Dubbelaar, {Marissa L.} and Holtman, {Inge R.} and {de Boer-Bergsma}, Jelkje and Eggen, {Bart J. L.} and Boddeke, {Hendrikus W. G. M.} and {De Deyn}, {Peter P.} and {Dam, van}, Debby",

year = "2017",

month = feb,

doi = "10.1016/j.bbadis.2016.11.014",

language = "English",

volume = "1863",

pages = "395--405",

journal = "Biochimica et biophysica acta-Molecular basis of disease",

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number = "2",

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Janssen, L, Dubbelaar, ML, Holtman, IR, de Boer-Bergsma, J, Eggen, BJL , Boddeke, HWGM , De Deyn, PP & Dam, van, D 2017, 'Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease', Biochimica et biophysica acta-Molecular basis of disease, vol. 1863, no. 2, pp. 395-405. https://doi.org/10.1016/j.bbadis.2016.11.014

Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease. / Janssen, Leen; Dubbelaar, Marissa L.; Holtman, Inge R. et al.
In: Biochimica et biophysica acta-Molecular basis of disease, Vol. 1863, No. 2, 02.2017, p. 395-405.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Aging, microglia and cytoskeletal regulation are key factors in the pathological evolution of the APP23 mouse model for Alzheimer's disease

AU - Janssen, Leen

AU - Dubbelaar, Marissa L.

AU - Holtman, Inge R.

AU - de Boer-Bergsma, Jelkje

AU - Eggen, Bart J. L.

AU - Boddeke, Hendrikus W. G. M.

AU - De Deyn, Peter P.

AU - Dam, van, Debby

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Gene expression

KW - RNA sequencing

KW - Amyloid

KW - APP23 mouse model

KW - Inflammation

KW - AMYLOID PRECURSOR PROTEIN

KW - DENDRITIC SPINE MORPHOGENESIS

KW - GENE-EXPRESSION DATA

KW - TRANSGENIC MICE

KW - BETA-PROTEIN

KW - SYNAPTIC PLASTICITY

KW - SWEDISH MUTATION

KW - CATHEPSIN-B

KW - ACTIN CYTOSKELETON

KW - MISSENSE MUTATIONS

U2 - 10.1016/j.bbadis.2016.11.014

DO - 10.1016/j.bbadis.2016.11.014

M3 - Article

SN - 0925-4439

VL - 1863

SP - 395

EP - 405

JO - Biochimica et biophysica acta-Molecular basis of disease

JF - Biochimica et biophysica acta-Molecular basis of disease

IS - 2

ER -