THIS image by Dominik Paquet of Ludwig-Maximilians-Universität in Munich is one of the winners of the 2009 Nikon Small World Photomicrography competition. It's a confocal fluoresence microscopy image of zebrafish larvae expressing a mutant form of human Tau protein, which forms the neurofibrillary tangles that are a pathological hallmark of Alzheimer's Disease. The work is described in this recent paper.
Below are two more images from the competition.
This image of pyramidal cells in the mouse cerebral cortex was created by Celine Plachez of the University of Maryland School of Medicine. These are among the largest in the mammalian brain. First discovered by the great Spanish neuroanatomist Santiago Ramón y Cajal, they are so called because of their characteristic triangular cell body. Pyramidal cells are the brain's projection neurons, with axons that extend long distances. Most project from one region of the brain to another, and those in the motor cortex descend in the spinal cord to form connections with the neurons which control voluntary movement.
Finally, there's this image of Purkinje cells in the mouse cerebellum, by Alan Opsahl of Pfizer. These are also among the largest cells in the brain. They have a planar, or two-dimensional, structure, with an extensive dendritic tree that forms synapses with hundreds of thousands of parallel fibres, and an axon which projects down into the deep cerebellar nuclei. The information propagated along their axons is related to motor co-ordination and fine control of movement, is the sole output of the cerebellum.
Beautiful imaging, and, in the fish model, an innovative way of identifying the affected subjects. However, Alzheimer's shows not in young people, but in old age. When one peruses the paper it is shown that the symptoms begin in larval fish, not in mature ones. Is this a valid model in which to test drugs after all? It seems that the genetic manipulation has turned Alzheimer's from a disease of old age into a developmental disability.
Now, back in the dark ages (about 20 years ago) when I was working with folks who were developmentally disabled, there was a connection noted between Down's Syndrome and Alzheimer's Disease; more than 50% of the folks with non-mosaic Down's who survived past, say, 45 or so would get Alzheimer's, and their prognoses were especially grim. Perhaps these folks with the fish have once more found that connection inadvertently.
They're interested more in mechanisms of cell death than in disease symptoms, and although no animal model is ideal, I think this one's quite good for that purpose. The cellular pathology is recapitulated, and dying cells can be viewed directly and in their natural environment, because the larvae are transparent. The model also allows for quick, large-scale screening of compounds in vivo. Promising compounds can be tested further in other animals such as mice.
Down's is linked to APP, not Tau. The APP gene is located on chromosome 21, so Down's patients have an extra copy. Their increased risk for Alzheimer's might therefore be related to elevated levels of APP and amyloid beta, the insoluble 42 amino acid APP fragment which is deposited as plaques in AD, and which is apparently toxic to neurons. The transgenic zebrafish don't express APP, so I don't know what they can tell us about early onset of AD in Down's patients.
In mere aesthetics terms the images are stunning.
For an old comparison study of the link between Alzheimer and Down syndrome (The pathological association between Down syndrome and Alzheimer disease) the study suggests that at middle age the Down patients resemble Alzheimer dementia-type for the pathophysiological reasons you mention Mo.
Beautiful! This is scientific art! Or artistic science!