Loss of neurons in the hippocampus and other brain regions is, besides the occurrence of plaques and tangles, a neuropathological feature of Alzheimer's disease (AD). In recent years a plethora of transgenic mouse models overexpressing mutant amyloid precursor protein (APP) has been developed, which represent valuable research tools. Whereas extracellular plaque pathology is a common feature of these models, neuronal loss is a rather rare characteristic. In the present study, we quantified the number of neurons in the dentate gyrus granule layer (GCL) in 2- and 12-month-old APP/PS1KI mice, a mouse model that has been previously shown to have significant loss of neurons in the CA1 layer of the hippocampus. Stereological analysis revealed a strongly significant decrease of GCLs in aged APP/PS1KI mice, compared to age-matched PS1KI control animals (-44%), however, the volume of the GCL was not different.
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http://dx.doi.org/10.1016/j.brainres.2008.05.052 | DOI Listing |
Alzheimers Res Ther
October 2017
Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
Background: The deposition of neurotoxic amyloid-β (Aβ) peptides in plaques in the brain parenchyma and in cerebral blood vessels is considered to be a key event in Alzheimer's disease (AD) pathogenesis. Although the presence and impact of full-length Aβ peptides such as Aβ and Aβ have been analyzed extensively, the deposition of N-terminally truncated Aβ peptide species has received much less attention, largely because of the lack of specific antibodies.
Methods: This paper describes the generation and characterization of novel antibodies selective for Aβ peptides and provides immunohistochemical evidence of Aβ in the human brain and its distribution in the APP/PS1KI and 5XFAD transgenic mouse models.
Mol Neurobiol
January 2017
Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, von-Siebold-Str. 5, Goettingen, 37075, Germany.
The epsilon 4 allele of the apolipoprotein E (ApoE4) gene is the most important risk factor implicated in Alzheimer's disease (AD) etiology. ApoE4 is more susceptible to proteolysis, and ApoE fragments have been shown to promote tau hyperphosphorylation and exert neurotoxic properties. While a plethora of studies deals with the effect of ApoE and its fragments on amyloid-β peptide (Aβ) deposition and clearance, it is largely unknown whether Aβ in turn influences human or murine ApoE expression and its proteolysis.
View Article and Find Full Text PDFJ Alzheimers Dis
November 2016
Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by early intraneuronal amyloid-β (Aβ) accumulation, extracellular deposition of Aβ peptides, and intracellular hyperphosphorylated tau aggregates. These lesions cause dendritic and synaptic alterations and induce an inflammatory response in the diseased brain. Although the neuropathological characteristics of AD have been known for decades, the molecular mechanisms causing the disease are still under investigation.
View Article and Find Full Text PDFSolanezumab and Crenezumab are two humanized antibodies targeting Amyloid-β (Aβ) which are currently tested in multiple clinical trials for the prevention of Alzheimer's disease. However, there is a scientific discussion ongoing about the target engagement of these antibodies. Here, we report the immunohistochemical staining profiles of biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab in human formalin-fixed, paraffin-embedded tissue and human fresh frozen tissue.
View Article and Find Full Text PDFFront Aging Neurosci
July 2014
Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University Goettingen, Germany.
Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI).
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