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Morphological and Cellular Aspects of the Aging Brain

Morphological and Cellular Aspects of the Aging Brain

Teaser: 

John R. Wherrett, MD, PhD, FRCPC, Department of Medicine (Neurology), Toronto Western Hospital and University of Toronto, Toronto, ON.

Contemporary technologies, including digital imaging of the brain during life and quantative microscopy (unbiased stereology) for estimating histological features postmortem, have resulted in important new knowledge about changes in the brain that accompany healthy aging, including evidence that grey matter atrophies with an anterior-posterior gradient. Neurons shrink but numbers are preserved; however, there is moderate reduction in dendritic spines and in synapses that have altered function. This is to be interpreted in the light of evidence for neurogenesis continuing into late life. White matter volume increases into maturity, but in aging there is a marked reduction due mostly to a loss of small myelinated fibres. Cell inclusions characteristic of neurodegenerative disease are commonly found postmortem in the healthy aged.
Key words: brain, aging, morphometry, imaging.

Cerebrovascular Pathologies in Alzheimer Disease

Cerebrovascular Pathologies in Alzheimer Disease

Teaser: 

John Wherrett, MD, FRCPC, PhD, Division of Neurology, Toronto Western Hospital and the University of Toronto, Toronto, ON.

This commentary addresses current views about the interaction of vascular disorders and Alzheimer disease, including vascular pathologies that may be intrinsic to the Alzheimer process as identified through demonstration of amyloid plaques and neurofibrillary tangles. The common cerebrovascular pathologies accompanying aging, mainly atherosclerosis and arteriosclerosis, will coincide in varying proportions with the Alzheimer pathology, also a concomitant to aging. Because interventions are available to modify both risks and complications of these vasculopathies, an important goal of dementia research is to develop means to characterize the contribution of cerebrovascular disease in Alzheimer and other dementias. Realization of this goal is confounded by the recognition that Alzheimer pathology, usually considered a parenchymal process, involves important vascular changes.
Key words: Alzheimer disease, dementia, cerebrovascular, pathology, imaging.

Breakthrough in Cellular Level Functional Imaging--Broad Implications for Medical and Aging Research

Breakthrough in Cellular Level Functional Imaging--Broad Implications for Medical and Aging Research

Teaser: 

Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging

In a stunning presentation at the National Academy of Engineering meeting, Thomas J. Meade of the California Institute of Technology presented frog embryos unfolding from egg to tadpole stages. The images provided an unprecedented degree of cellular resolution, allowing one to see a cell reacting to alterations in a single gene. The technique perfected by Meade and his colleagues represents a major advance in functional nuclear magnetic resonance (NMR) technology.

Positron Emission Tomography (PET) and functional magnetic resonance imaging (fMRI) are both known to reveal sites in the living brain or other tissues that are active when a person is engaged in performing a particular task. These techniques have provided an extraordinary amount of biological information and are among the most important advances in medical science.

The Meade technique uses a novel contrast agent that identifies specific cells when their genes are turned on. NMR relies on the detection of vibrations in hydrogen atoms of water that are induced by a magnetic field. Contrast agents, such as gadolinium, are often added to enhance hydrogen's signal emission. This technique provides a powerful means to image the topography of soft tissue, but cannot provide a deeper level of resolution.

Meade has discovered an elegant and economical solution to one of the most significant problems in biological science: how to provide functional images of cellular level activity. He solved this problem by constructing a 'molecular basket' for each gadolinium ion. The basket consists of claw-like molecules called chelators. He then created a lid for the basket made out of galactopyranose. The 'closed basket' was injected into both cells of a two-cell frog embryo. One of the two cells was also injected with the gene for galactopyranose-digesting enzyme. Upon synthesis of the galactopyranose-digesting enzyme, the galactopyranose 'lid' was digested, exposing gadolinium to water, resulting in a bright signal. The principle of this technique can potentially be used for detecting any enzyme. Thus, one can create a general method for tracking the changes in any cell, or cellular pathway. Even more exciting is research aimed at finding a way of attaching a drug to the 'basket' and activating it with a particular enzyme within a cell. The potential for this new delivery system is enormous.

Advances in aging research will require understanding the activities and interactions of hundreds of genes. The ability to resolve functional NMR images down to the cellular level will have enormous implications for this research.