A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

Neurodegeneration of the retina in mouse models of Alzheimer’s disease: what can we learn from the retina?

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease commonly found among elderly. In addition to cognitive and behavioral deficits, vision abnormalities are prevalent in AD patients. Recent studies investigating retinal changes in AD double-transgenic mice have shown altered processing of amyloid precursor protein and accumulation of β-amyloid peptides in neurons of retinal ganglion cell layer (RGCL) and inner nuclear layer (INL). Apoptotic cells were also detected in the RGCL. Thus, the pathophysiological changes of retinas in AD patients are possibly resembled by AD transgenic models. The retina is a simple model of the brain in the sense that some pathological changes and therapeutic strategies from the retina may be observed or applicable to the brain. Furthermore, it is also possible to advance our understanding of pathological mechanisms in other retinal degenerative diseases. Therefore, studying AD-related retinal degeneration is a promising way for the investigation on (1) AD pathologies and therapies that would eventually benefit the brain and (2) cellular mechanisms in other retinal degenerations such as glaucoma and age-related macular degeneration. This review will highlight the efforts on retinal degenerative research using AD transgenic mouse models

Independent neural mechanisms for bright and dark information in binocular stereopsis.

Early visual processing is organized into a number of independent channels. In the retina, increments and decrements of brightness are processed independently by different groups of neurons. For psychophysical measurements of human vision, independence can be tested statistically. Using this criterion in a depth judgement task, we show here that, for binocular stereo vision, increments and decrements are treated independently, at least as far as the level at which information from the left and right eyes is first combined. At later stages of stereo processing, the information from the two channels is no longer independent. Because the signals for stereo vision are first combined at the visual cortex, these results suggest that the neural 'on' and 'off' channels remain independent right up to early cortical stages. Theoretical studies of stereo vision have proposed that visual features in the views of the two eyes are matched on the basis of 'similarity'. Our results show that stereo matching treats features as statistically independent (and therefore dissimilar) if they appear perceptually bright and dark relative to the background. If features differ perceptually but only in the degree of brightness or darkness, human stereo vision treats them as similar