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Changes in extracellular space size and geometry in APP23 transgenic mice: A model of Alzheimer's disease

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Syková, Eva, Voříšek, Ivan, Antonova, Tatiana, Mazel, Tomáš, Meyer-Luehmann, Melanie, Jucker, Mathias, Hájek, Milan, Or, Michael +1 more·2005·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0408235102PMC PMC544312
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Abstract

Diffusion parameters of the extracellular space (ECS) are changed in many brain pathologies, disturbing synaptic as well as extrasynaptic “volume” transmission, which is based on the diffusion of neuroactive substances in the ECS. Amyloid deposition, neuronal loss, and disturbed synaptic transmission are considered to be the main causes of Alzheimer's disease dementia. We studied diffusion parameters in the cerebral cortex of transgenic APP23 mice, which develop a pathology similar to Alzheimer's disease. The real-time tetramethylammonium (TMA) method and diffusion-weighted MRI were used to measure the ECS volume fraction (α = ECS volume/total tissue volume) and the apparent diffusion coefficients (ADCs) of TMA (ADC TMA ), diffusing exclusively in the ECS and of water (ADC W ). Measurements were performed in vivo in 6-, 8-, and 17- to 25-month-old hemizygous APP23 male and female mice and age-matched controls. In all 6- to 8-month-old APP23 mice, the mean ECS volume fraction, ADC TMA , and ADC W were not significantly different from age-matched controls (α = 0.20 ± 0.01; ADC TMA , 580 ± 16 μm 2 ·s -1 ; ADC W , 618 ± 19 μm 2 ·s -1 ). Aging in 17- to 25-month-old controls was accompanied by a decrease in ECS volume fraction and ADC W , significantly greater in females than in males, but no changes in ADC TMA . ECS volume fraction increased (0.22 ± 0.01) and ADC TMA decreased (560 ± 7 μm 2 ·s -1 ) in aged APP23 mice. The impaired navigation observed in these animals in the Morris water maze correlated with their plaque load, which was twice as high in females (20%) as in males (10%) and may, together with changed ECS diffusion properties, account for the impaired extrasynaptic transmission and spatial cognition observed in old transgenic females.

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  • Amyloid deposition damages the ECM scaffold.

    “Amyloid deposition damages the ECM scaffold (Ajmo et al., 2010, Sykova et al., 2005).”

    From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Sykova et al., 2005

    The Discussion links possible loss of extracellular matrix molecules to aging in control mice, and separately describes amyloid plaques and altered extracellular-space properties in APP23 mice. The passages searched do not say that amyloid deposition damages the extracellular matrix scaffold. (LLM, conf=0.73)

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Authors
Syková, E., Voříšek, I., Antonova, T., Mazel, T., Meyer-Luehmann, M., Jucker, M., Hájek, M., Or, M., & Bureš, J.
Affiliations
  • Czech Academy of Sciences (CZ)
  • Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic; Department of Neuroscience and Center for Cell Therapy and Tissue Repair, Charles University, Second Medical Faculty, Vúvalu 84, 150 06 Prague 5, Czech Republic; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried-Muller Strasse 27, D-72076 Tübingen, Germany; Department of Radiology, Institute for Clinical and...
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2005-01-03
Volume
102
Issue
2
Pages
479-484
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0408235102
PMC
PMC544312
OpenAlex
W2004485166
Cited by
121
References
5
Citations by year
2026: 1 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 12 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 11 · 2012: 6
FWCI
3.41
Type
journal article
Language
en
Update notices
correction (2005-02-01)
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
extracellular space, APP23 transgenic mice, Alzheimer's disease model, cerebral cortex, apparent diffusion coefficient, tetramethylammonium, amyloid plaques, aging, sex differences, spatial cognition, diffusion-weighted imaging
MeSH terms
Aging, Alzheimer Disease, Quaternary Ammonium Compounds, Animals, Diffusion, Disease Models, Animal, Extracellular Space, Female, Magnetic Resonance Imaging, Male, Mice, Transgenic, Amyloid beta-Protein Precursor, Mice

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