Cited by 65Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Abeta deposition and related pathology in an APP x PS1 transgenic mouse model of Alzheimer's disease.

Howlett·2008·PubMed

Abstract

A transgenic mouse bearing mutant transgenes linked to familial forms of Alzheimer's disease (AD) for the amyloid precursor protein and presenilin-1 (TASTPM) showed Abeta plaque deposition and age-related histological changes in associated brain pathology. The Abeta present was of multiple forms, including species with a C-terminus at position 40 or 42, as well as an N-terminus at position 1 or truncated in a pyro-3-glutamate form. Endogenous rodent Abeta was also present in the deposits. Laser capture microdissection extracts showed that multimeric forms of Abeta were present in both plaque and tissue surrounding plaques. Associated with the Abeta deposits was evidence of an inflammatory response characterised by the presence of astrocytes. Also present in close association with the deposits was phosphorylated tau and cathepsin D immunolabelling. The incidence of astrocytes and of phosphorylated tau and cathepsin D load showed that both of these potential disease markers increased in parallel to the age of the mice and with Abeta deposition. Immunohistochemical labelling of neurons in the cortex and hippocampus of TASTPM mice suggested that the areas of Abeta deposition were associated with the loss of neurons. TASTPM mice, therefore, exhibit a number of the pathological characteristics of disease progression in AD and may provide a means for assessment of novel therapeutic agents directed towards modifying or halting disease progression.

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OpenAlex · 10.14670/hh-23.67

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Authors
Howlett
Venue
PubMed
Publisher
National Institutes of Health
Published
2008-01-01
Volume
23
Issue
1
Pages
67-76
OpenAlex
W439849972
Cited by
65
References
32
Citations by year
2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2013: 4 · 2012: 6
FWCI
4.51
Type
journal article
Language
en
Open access
closed
Locations
  • PubMed (publishedVersion)
  • PubMed
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, amyloid-beta deposition, APP/PS1 mice, amyloid precursor protein, presenilin 1, amyloid plaques, astrocytes, neuroinflammation, phosphorylated tau, cathepsin D, neuronal loss, disease markers, familial Alzheimer's disease
MeSH terms
Alzheimer Disease, Animals, Cathepsin D, Cerebral Cortex, Disease Models, Animal, Hippocampus, Male, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Disease Progression, Mice, Presenilin-1

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