Intraneuronal Aβ accumulation and neurodegeneration: Lessons from transgenic models

• Published in: Life sciences (1973) 2012-12, Vol.91 (23-24), p.1148-1152
• Main Authors: Wirths, Oliver, Bayer, Thomas A.
• Format: Article
• Language: English
• Subjects: Alzheimer; Alzheimer disease; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid; Amyloid beta-Peptides - immunology; Amyloid beta-Peptides - metabolism; animal models; Animals; antibodies; Antibodies - immunology; Disease Models, Animal; genetically modified organisms; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Intraneuronal Abeta; Mice; Mice, Transgenic; Neuron loss; neurons; Neurons - metabolism; Neurons - pathology; peptides; Transgenic mice
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2012.02.001

In the present review we summarize current knowledge on the concept of intraneuronal Aβ as a determinant for neuron loss and other pathological alterations in transgenic models for Alzheimer disease. We discuss the use of transgenic mouse and non-vertebrate transgenic models accumulating intracellular Aβ peptides and their impact on the ongoing discussion. Intraneuronal Aβ accumulation in transgenic models is intimately linked to pathological alterations including neuron loss. One of the technical caveats for visualizing intraneuronal Aβ is the antibody used to unequivocally demonstrate its presence. Very often antibodies were used that recognize both Aβ and APP, leading to false positive results due to misinterpretation. Whereas a clear relationship between intraneuronal Aβ accumulation and neuron loss is evident in transgenic mouse models it remains an unresolved issue whether the concept of intraneuronal Aβ can be integrated into the human pathology as well.