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

Summary. 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 Aß plaque deposition and age-related histological changes in associated brain pathology. The Aß 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 Aß was also present in the deposits. Laser capture microdissection extracts showed that multimeric forms of Aß were present in both plaque and tissue surrounding plaques. Associated with the Aß 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 Aß deposition. Immunohistochemical labelling of neurons in the cortex and hippocampus of TASTPM mice suggested that the areas of Aß 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

The oviduct in chaos

The unilateral avian oviduct is divisible into five functional regions which, moving distally, include the infundibulum, magnum, isthmus, tubular shell gland and shell gland pouch. Each region subserves a variety of functions, which through their interaction give rise to the multilayered albumen, shell membranes and the organichnorganic complex, which comprises the shell. The sequential activity of these structurally diverse regions is a necessary prerequisite for "normal" egg formation. The reproductive effort can be influenced by a number of disease processes either directly by virtue of the fact that they alter the ability of the lining cells to synthesise their integral components or indirect by generally compromising bird health. Notable amongst the former are Infectious Bronchitis, Newcastle Disease and Egg Drop Syndrome. All change the quality of the final product in terms of the shape and texture of the shell. In recent years it has become evident that environmental stress has an equally, if not more, important role to play in oviduct disfunction. In the absence of large areas of functional surface epithelium, the eggs laid were structurally defective at all levels from the mammillary layer outwards. As the epithelial layers regenerated, shell quality approximated normality, but never returned to the pre-stress condition. The process of candling signals amongst other internal defects a variety of inclusions variously classified as blood and meat spots. They are quite specific in their locations; thus blood spots originating from the rupture of ovarian blood vessels at ovulation, are invariably confined to the periphery of the yolk mass, while meat spots now classified according to their composition are confined to albumen. Within the latter they are recognised as tissue rich deposits, the result of oviduct breakdown and/or calcium rich fragments. The latter implies a breach in the barrier provided by the soft shell membranes