title: Stereological estimation of neuron number and plaque load in the hippocampal region of a transgenic rat model of Alzheimer's disease.
abstract: The main hallmarks of Alzheimer's disease (AD) are senile plaques, neurofibrillary tangles and neuronal death. The McGill-R-Thy1-APP rat is one of the few transgenic rat models of AD that displays progressive amyloid pathology. This study aimed to further characterise this rat model, focusing on the pathological changes in the hippocampal formation and the parahippocampal region. These structures, that are important for episodic memory and spatial navigation, are affected in the early stages of the disease. This study used unbiased stereology to investigate possible neuronal loss in the CA1, subiculum and entorhinal cortex of 18-month-old homozygous McGill-R-Thy1-APP rats, and also quantified the plaque load in all the areas of the hippocampal formation and parahippocampal region from 9 to 18 months old. A significant reduction of neurons at 18 months was only seen in the subiculum. The first plaque pathology was seen at 9 months in the subiculum. Although the quantified plaque load was variable between animals, the pattern of spatiotemporal progression was similar for all animals. The spread of plaque pathology mainly affected anatomically connected regions. Overall, the plaque pathology observed in the transgenic rats was similar to the early phases of amyloid beta (Aβ)-deposition described in human patients. The findings here thus indicate that the McGill-R-Thy1-APP rat could be a good model of the Aβ pathology in AD, but less so with respect to neuron loss.
authors: Kavli Institute for Systems Neuroscience & Centre for Neural Computation, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Postboks 8905, 7491, Trondheim, Norway.
authors: Ingrid
authors: I
authors: Heggland
authors: Inge S
authors: IS
authors: Storkaas
authors: Hanne T
authors: HT
authors: Soligard
authors: Asgeir
authors: A
authors: Kobro-Flatmoen
authors: Menno P
authors: MP
authors: Witter
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000473:pathology*; D005260:Female; D006720:Homozygote; D008297:Male; D009474:Neurons / Q000473:pathology*; D009928:Organ Specificity; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: amyloid plaques; cell loss; entorhinal cortex; hippocampus; subiculum