A website entitled "The fine structure of the aging brain".

In the spirit of sharing knowledge we decided to provide the means by which these images can be downloaded for educational purposes. The images are grouped into chapters, and users can download the images from each chapter (at a resolution of 6×9” at 240 dpi), but in addition, we have provided a download page so that users can obtain even higher resolution images (most of them 6×7” at 600 dpi) free of labeling and text. All images are available from our website, http://www.bu.edu/agingbrain. We have not included images of the structural appearance of components of cells and their processes in young monkeys, as such images can be found in the illustrations in the book, “The Fine Structure of the Nervous System: Neurons and Their Supporting Cells” 1991, by Alan Peters, Sanford L. Palay, and Henry deF. Webster, 3rd Edition, Oxford University Press. The reason for choosing to study the effects of normal aging in rhesus monkeys is that these primates provide a good model for understanding and interpreting the effects of normal aging in human brains. Unlike the short-lived rodents, for example, in monkeys the effects of aging extend over many years. Indeed, the life span of rhesus monkeys closely approaches that of humans, since these monkeys live to a maximum of about 35 years. So that if humans are considered to live for about 100 years of age, then one monkey year is equivalent to about 3 human years. Another important consideration for studying the effects of normal aging on the brains of rhesus monkeys is these monkeys do not develop Alzheimer's disease, so that the effects of normal aging are not confounded by pathological changes that might occur during the early stages of Alzheimer's disease. Some senile plaques do occur in the cerebral cortices of rhesus monkeys, but the plaques are few in number and their frequency does not correlate with cognitive decline. Moreover, rhesus monkeys have complex behavior patterns that approach those of humans, so that behavioral tests similar to those used in humans can be employed to accurately assess their cognitive status before their brains are preserved for structural evaluations. This means that determinations can be made about whether the frequency of occurrence of a particular age-related fine structural alteration does or does not correlate with cognitive decline. The brain tissue used in our studies has been fixed by perfusion of aldehyde containing solutions through the heart. Tissue blocks were then taken, osmicated and embedded in Araldite for thin sectioning. The thin sections were stained with lead citrate and uranyl acetate, before being photographed in an electron microscope. The 3×4” sheet film negatives were then scanned at high resolution and stored in a computer. The 130 electron micrographs in this website are presented in 18 chapters, each chapter being devoted to a particular component of the brain, and each chapter has a brief introduction to explain something about the images that are being presented within it. The images have minimal labeling, and some of the micrographs have colored versions. These colored versions show the distribution and relationships of the various components of the neuropil, and to help in interpretation of the images, as far as possible a standardized color scheme has been used throughout. Figures 1 and ​and22 show representative examples from this resource. Figure 1 Plate 14.5: A microglial cell in the primary visual cortex of a 35 year old monkey. Note the phagocytosed material at the two poles of the perikaryon (arrows). Figure 2 Plate 15.2: A large hole lying adjacent to a neuronal cell body in the neuropil of layer 3 in the primary visual cortex of a 35 year old monkey. This hole contains membranous debris and may represent a degenerating dendrite or neuronal cell body. It should be pointed out that to date very few parts of the non-human primate brain have been examined to determine the effects of normal aging on the central nervous system. And furthermore only a few studies have been carried out in which the tissue being examined is from primates that have been behaviorally tested to determine their cognitive status. As far as gray matter is concerned, aging studies have been largely confined to area 46 of the prefrontal cortex and to the primary visual cortex, area 17, with a few observations on dentate gyrus, and on the Betz cells in motor cortex. More is known about the effects of aging on white matter, since the fine structure of nerve fibers has been examined in a number of well-circumscribed fiber bundles in the cerebral hemispheres. Reviews of the results of these studies can be found in the reviews by Peters and Kemper (2012) and Morrison and Baxter (2012). A summary of what is known about the effects of aging on the morphological integrity of the primate brain is as follows: A number of structural factors, such as the total volume of the brain, the numbers of neurons, and astrocytes and microglial cells in various parts of the brain, do not appear to alter significantly with increasing age. Some structural alterations increase with frequency with age, but the frequency does not correlate with cognitive decline. Among these alterations are age-related losses of nerve fibers that are 20% or lower, and an increased frequency of degenerating myelin sheaths in some fiber tracts. Other alterations in this category are an increase in the frequency of senile plaques; an increase in frequency of oligodendrocytes; and the loss of synapses from the lower layers of the prefrontal cortex. Among the structural alterations that increase in frequency with age, and the frequency of which correlate with cognitive decline, are the following: an increased frequency of degenerating myelin sheaths, the loss of substantial numbers of nerve fibers from some fiber tracts, and the loss of synapses and dendritic spines from the upper layers of prefrontal area 46. What is becoming clear is that the cognitive decline that occurs during normal aging is not attributable to a single factor, and that while degenerative alterations are occurring some repair is also taking place. The most obvious example of repair is the remyelination that leads to the formation of more numerous and shorter internodal lengths of myelin, and the increased numbers of oligodendrocytes that are generated to effect this repair. Obviously, this is only a beginning in our understanding the effects of aging on the primate brain. In the future, additional cortical areas need to be examined to determine if alterations, such as the synapse losses from the upper layers of area 46 of the cortex, are specific to that area or whether synaptic losses occur throughout the cortex. If synaptic losses are ubiquitous, the origins of the axon terminals that degenerate to account for the losses must be determined.