Brain Plasticity and Alzheimer’s Disease

(Society for Neuroscience) The discovery that the human brain can produce new cells in adulthood offers just one example of how adaptable the brain is throughout life. With this knowledge, researchers are investigating how normal aging as well as neurodegenerative diseases like Alzheimer’s disease affect that adaptability, and how we can maintain healthy brain function as our brains age. Future research may one day allow scientists to capture the adult brain’s enormous capacity to adapt in order to help prevent or perhaps even reverse memory-robbing Alzheimer’s disease.

The Discovery: The Brain is Adaptable Throughout Life

When scientists discovered that the brain could create new brain cells in adulthood, they introduced a new way of thinking that could one day help treat or delay onset of Alzheimer’s disease (AD). AD is the most common form of cognitive dementia, the loss of higher mental functions like memory.

The image shows the addition of new neurons in the adult  mouse hippocampus — the brain region involved in learning and memory. This birth of  new cells is a major finding in showing how adaptable the brain is, even in adulthood. (Brain cells labeled blue-green are eight weeks old, while cells labeled red are at most four  weeks old.) Credit: Reprinted with permission from Gage, F. and Zhao, C. Laboratory of  Genetics LOG-G; The Salk Institute for Biological Studies. 2007.

New Discovery, New Belief

Researchers in the 1960s were curious to understand more about growth and repair in the adult brain, and conducted a number of experiments with rodents to help illuminate these processes. They made an amazing and unexpected discovery: newly created cells that later transformed into what appeared to be neurons, or brain cells.

The discovery was not initially recognized for the breakthrough it was because most experts thought that the brain finished developing and changing early in life and did not produce more neurons. Additionally, scientists faced the challenge of proving that the newly created cells were neurons.

Further advances came from explorations of learning conducted by researchers lured by birdsong. Years after the initial discoveries, advanced brain imaging techniques helped establish the existence, in adult canaries, of these precursor cells, or stem cells, that reproduced, migrated to other brain areas, and matured into neurons. This process, called neurogenesis, is just one example of how plastic or adaptable the brain is.

Human Discoveries

Further research has proved that the brains of adult humans also undergo neurogenesis, revealing the plasticity of the brain throughout our lives. Scientists located adult human neurogenesis sites in the dentate gyrus of the hippocampus — the brain region involved in learning and memory — and the subventricular zone in the region where fluid that helps protect the brain and spinal cord is made.

Indeed, scientists worldwide, working in many different specialties, have found that the human brain is highly plastic, possessing the ability not only to create new neurons, but to modify networks of neurons to better cope with new circumstances.

These collective discoveries may pave the way for further understanding of how old age and conditions like AD affect plasticity, and may help researchers find ways to preserve it.

New Application: Enhancing the Brain’s Plasticity

Once scientists realized the adult brain’s enormous capacity for plasticity, they could study the effects of aging and Alzheimer’s disease on that capability and explore ways to maintain healthy brain function.

Left: These three-dimensional projections of brain positron emission tomography scans (outer brain surface) show amyloid plaques and tau tangles labeled by a chemical marker — the first developed to tag physical evidence of Alzheimer’s disease (AD) in living people. The control image is from an older person without AD. Warmer colors (red, yellow)indicate higher levels of plaques and tangles. Credit: Reprinted from Lancet Neurology, 7, G. Small et al., Current and future uses of neuroimaging for cognitively impaired patients, 161–72, © (2008), with permission from Elsevier.

Right: This figure shows the effects of exercise on levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of rats. Growth factors like BDNF help many neurons survive. Levels of the message that makes BDNF are much higher in exercising rats(A) than in sedentary animals (B). Red and yellow denote the highest level of BDNF, while green and blue denote the lowest. Credit: Alzheimer’s Disease Education and Referral Center, a service of the National Institute on Aging.

Declining Plasticity in Old Age and in People with Alzheimer’s Disease

Brain deterioration begins well before old age. Scientists believe that changes in plasticity at brain synapses — the junctions where neurons signal to each other — and the loss of neurons may be responsible for this decline in function.

Interestingly, these changes also precede AD impairments and many harmful precursors of AD, like amyloid beta deposits, tau tangles, ApoE4 proteins, and brain inflammation. These AD hallmarks damage areas of the brain responsible for learning, memory, and cognition by further impairing synapses and contributing to cell death. With AD patients, early neuron loss and changes in synapse function have been observed in the hippocampus and neocortex — the very brain regions involved in language, memory, and other higher cognitive functions.

An Enriched Environment Plays a Role

Researchers have found at least one clear link between brain plasticity and healthy aging: They know that a rich, stimulating environment can enhance and maintain brain plasticity, even in old age and with AD patients. Studies of aged rodents modeled with and without AD show that regular social interaction, exercise, and a healthful diet, as well as cardiovascular exercise, can increase neurogenesis, neuron communication, and hippocampus-related learning, and can decrease levels of amyloid beta deposits. In addition, exercise has been shown to help increase production of proteins and blood vessels that support the growth and survival of cells.

In humans, research has revealed that exercise enhances cognitive function and protects against dementia and neurodegenerative diseases like AD — just one line of discovery that shows promise against these debilitating conditions.

Health Implications: Promise for Treating Alzheimer’s Disease

With new knowledge of how normal aging and conditions like Alzheimer’s disease affect plasticity and how environment can enhance brain function, scientists can investigate the power of plasticity in treating AD.

As Alzheimer’s disease progresses, it kills brain cells mainly in the hippocampus and  cortex, which leads to impairments in learning, memory, and thinking. Harnessing the brain’s capacity to adapt in adulthood may one day help prevent and treat Alzheimer’s disease. Credit: Adapted and reprinted with permission from the Alzheimer’s Association. © 2008 Alzheimer’s Association. All rights reserved.

Maintaining Healthy Brain Function

Targeting areas in the brain that may be more vulnerable to aging and AD, such as the hippocampus, may enhance overall brain function and help slow or stop the natural decline in brain plasticity.

Using strategies to maintain healthy brain function in youth and increasingly in old age may also help delay or prevent decreasing brain plasticity. Cardiovascular exercise and other behavioral changes — such as switching to a more healthful diet — may stave off cognitive decline, keep brain networks flexible, increase neurogenesis, and enhance processes that aid in the growth and survival of both existing and new cells.  

Boosting Brain Plasticity as Treatment

For now, encouraging efforts to enhance brain plasticity at the first sign of neuron dysfunction, before AD impairments develop, may be the best bet in treating or delaying onset of the disease.

For example, brain plasticity exercises may one day help AD patients. These include demanding sensory, cognitive, and motor activities that reengage and strengthen the brain systems involved in learning. Such brain plasticity training has helped normal aging adults improve memory.

Many drug trials also are underway that target the early development of amyloid beta, tau, ApoE4, and brain inflammation to prevent or reverse their negative effects on brain plasticity and cell loss, and ultimately on learning and memory.

Researchers have much more to learn about preserving and enhancing plasticity as a way to defend against memory-robbing conditions that strike in old age. The discovery of adult neurogenesis is spurring significant progress, but only continued research will help scientists harness the adult brain’s enormous capacity for plasticity to prevent or delay the onset of AD, and to treat the more than 4.5 million Americans diagnosed with it.

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