Journal of Alzheimer's Disease - Volume 14, issue 2

Authors: Collingwood, Joanna F. | Chong, Ryan K. K. | Kasama, Takeshi | Cervera-Gontard, Lionel | Dunin-Borkowski, Rafal E. | Perry, George | Pósfai, Mihály | Siedlak, Sandra L. | Simpson, Edward T. | Smith, Mark A. | Dobson, Jon

Article Type: Research Article

Abstract: Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material – a hallmark of Alzheimer's disease pathology – in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes …are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain. Show more

Keywords: Alzheimer's disease, amyloid, electron microscopy, ferritin, imaging, iron, magnetite, senile plaque core, tomography

DOI: 10.3233/JAD-2008-14211

Citation: Journal of Alzheimer's Disease, vol. 14, no. 2, pp. 235-245, 2008

Authors: Lieberman, Andrew P. | Robins, Diane M.

Article Type: Review Article

Abstract: The androgen receptor (AR) is a ligand-activated transcription factor that is central to androgen-dependent development and diseases. Activity of the receptor is influenced by the length of a CAG/glutamine tract in its N-terminal transactivating domain. Expansions of this tract cause Kennedy disease, a protein aggregation degenerative disorder of motor neurons that occurs only in men, and shorter length tracts have been linked to increased risk of prostate cancer. Here we review recent data from mouse models in which gene targeting was used to humanize the mouse Ar gene and introduce CAG/glutamine tracts of varying lengths. Insertion of an expanded tract …encoded by 113 CAG repeats modeled Kennedy disease and revealed an important myopathic contribution to the disease phenotype. Variations in CAG tract length within the range of normal human alleles influenced the onset and progression of prostate cancer when targeted Ar mice were crossed to a transgenic prostate cancer model. This series of mice with different Ar alleles has provided insights into the mechanisms by which variations in the CAG/glutamine tract length influence the occurrence of human disease. Show more

Keywords: Androgen receptor, CAG/polyglutamine, Kennedy disease, mouse models, prostate cancer

DOI: 10.3233/JAD-2008-14212

Citation: Journal of Alzheimer's Disease, vol. 14, no. 2, pp. 247-255, 2008

Article Type: Announcement

DOI: 10.3233/JAD-2008-14213

Citation: Journal of Alzheimer's Disease, vol. 14, no. 2, pp. 257-258, 2008