Alzheimer disease models and human neuropathology: similarities and differences

Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Aβ peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Aβ peptide, similar but not identical to the Aβ peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Aβ, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Aβ 42 levels, except for the Arctic mutation, which alters the Aβ sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Aβ deposition in most mouse lines. Doubly (APP × mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Aβ. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Aβ oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau −/− background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Aβ or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis

Deep lamellar keratoplasty in the treatment of keratoconus

Copyright © 2006 S. Karger AG, BaselPurposeTo present our experience with a series of patients treated with deep lamellar keratoplasty (DLK) for keratoconus (KC).DesignA single surgeon, prospective, consecutive series.MethodThe study included all patients with KC who underwent DLK between March 1999 and November 2003 at the Royal Adelaide Hospital. The parameters evaluated included patients' demographics, pre- and post-operative best corrected visual acuities, post-operative keratometry, and intra- and post-operative complications.ResultsThere were 22 patients (23 eyes); 10 females and 12 males, with a mean age of 35 +/- 13 years (median, 33.5; range, 17-73). The median follow-up period was 13 months (range 7-38). In 89% (16/18) of eyes which underwent DLK, and in which a visual acuity could be obtained, a best corrected visual acuity of at least 6/12 was recorded. There were two episodes of Descemet's membrane perforation (8.7%), in which the procedure was converted to penetrating keratoplasty without complications. One patient developed a double anterior chamber, which resolved spontaneously without consequences.ConclusionThe visual outcomes and complication rates seen in our series are comparable to the recent published literature. Hence DLK can be considered as a suitable alternative to penetrating keratoplasty for the surgical treatment of KC.Nima Pakrou, Shirley Fung, Dinesh Selva, Mark Chehade, Igal Leibovitc