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Cited by 37Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Age-related changes of neuron numbers in the frontal cortex of a transgenic mouse model of Alzheimer’s disease

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Lemmens, Marijke A. M., Sierksma, Annerieke S. R., Rutten, Bart P. F., Dennissen, Frank, Steinbusch, Harry W. M., Lucassen, Paul J., Schmitz, Christoph·2011·Brain Structure and Function
DOI 10.1007/s00429-011-0305-1PMC PMC3155024
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Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by amyloid plaque accumulation, intracellular tangles and neuronal loss in selective brain regions. The frontal cortex, important for executive functioning, is one of the regions that are affected. Here, we investigated the neurodegenerative effects of mutant human amyloid precursor protein (APP) and presenilin 1 (PS1) on frontal cortex neurons in APP/PS1KI mice, a transgenic mouse model of AD, expressing two mutations in the human APP, as well as two human PS1 mutations knocked-in into the mouse PS1 gene in a homozygous (ho) manner. Although the hippocampus is significantly affected in these mice, very little is known about the effects of these mutations on selective neuronal populations and plaque load in the frontal cortex. In this study, cytoarchitectural changes were characterized using high precision design-based stereology to evaluate plaque load, total neuron numbers, as well as total numbers of parvalbumin- (PV) and calretinin- (CR) immunoreactive (ir) neurons in the frontal cortex of 2- and 10-month-old APP/PS1KI mice. The frontal cortex was divided into two subfields: layers II-IV and layers V-VI, the latter of which showed substantially more extracellular amyloid-beta aggregates. We found a 34% neuron loss in layers V-VI in the frontal cortex of 10-month-old APP/PS1KI mice compared to 2-month-old, while there was no change in PV- and CR-ir neurons in these mice. In addition, the plaque load in layers V-VI of 10-month-old APP/PS1KI mice was only 11% and did not fully account for the extent of neuronal loss. Interestingly, an increase was found in the total number of PV-ir neurons in all frontal cortical layers of single transgenic APP mice and in layers II-IV of single transgenic PS1ho mice between 2 and 10 months of age. In conclusion, the APP/PS1KI mice provide novel insights into the regional selective vulnerability in the frontal cortex during AD that, together with previous findings in the hippocampus, are remarkably similar to the human situation.

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  • In APP/PS1KI mice, significantly reduced CR- and PV-positive neuron numbers were found in the hippocampus, while no changes were detected in layers V and VI of the frontal cortex despite significantly reduced pyramidal neurons and massive thioflavin S-positive extracellular amyloid deposits.

    “A related finding was reported in APP/PS1KI mice, which presented with significantly reduced CR- and PV-positive neuron numbers in the hippocampus [125]. Interestingly, no changes were detected in layers V and VI of the frontal cortex in this model, although pyramidal neurons were significantly reduced and massive thioflavin S-positive extracellular amyloid deposits were present [129].”

    From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [129]

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Authors
Lemmens, M. A. M., Sierksma, A. S. R., Rutten, B. P. F., Dennissen, F., Steinbusch, H. W. M., Lucassen, P. J., & Schmitz, C.
Affiliations
  • Maastricht University (NL)
  • University of Amsterdam (NL)
  • Ludwig-Maximilians-Universität München (DE)
Corresponding author
Steinbusch, Harry W. M.
ORCID
Venue
Brain Structure and Function
Publisher
Springer Science and Business Media LLC
Published
2011-03-16
Volume
216
Issue
3
Pages
227-237
ISSN
  • 1863-2653 (ISSN-L)
  • 1863-2661
DOI
10.1007/s00429-011-0305-1
PMC
PMC3155024
OpenAlex
W1968781179
Cited by
37
References
63
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 3 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 1 · 2012: 4
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Brain Structure and Function (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by-nc)
  • UvA-DARE (University of Amsterdam) (publishedVersion, other-oa)
  • UvA-DARE (University of Amsterdam) (submittedVersion, other-oa)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • European Commission (MEST-CT-2005-020013)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91106003)
  • Internationale Stichting Alzheimer Onderzoek (MEST-CT-2005-020013)
  • Parkinsonfonden
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, frontal cortex, neuronal loss, amyloid plaques, amyloid-beta, parvalbumin neurons, presenilin 1, amyloid precursor protein, age-related neurodegeneration, regional vulnerability, cortical layers
MeSH terms
Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Frontal Lobe, Humans, Immunohistochemistry, Mice, Transgenic, Mutation, Nerve Degeneration, Neurons, Amyloid beta-Protein Precursor, Mice, Presenilin-1, Gene Knock-In Techniques

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