Today I'll point out a brace of recent research materials, all of which focus on the aging brain. A great deal of aging research is focused on the effects of aging in the brain, in part driven by the large level of investment in Alzheimer's disease research, and this overlaps with ongoing efforts to understand how the brain works: how it gives rise to the mind and how specific functional aspects of the mind work, all the way down to the level of proteins and intricate cellular structures such as synapses. While some researchers restrict themselves to investigation and observation, trying to fill in the large blank spaces on the map of the brain, others are working to find ways to repair some of the damage and reverse some of the declines. Forms of cell therapy are perhaps the closest to being broadly useful at the present time, but all sorts of ways to clear out cellular garbage and unwanted metabolic waste - such as the amyloid associated with Alzheimer's disease - are headed in the general direction of viability for clinical development.
Not this year, but certainly within the next decade, new classes of treatment will arrive, therapies that can at least partially address some of the fundamental causes of functional decline in the aging brain, rather than trying to patch over the consequences as so much of present day medicine does. Initially these therapies will be highly restricted, available only in trials, or for patients in the late stages of neurodegenerative conditions. That is the outcome that the current regulatory system forces upon us. There will be a mild but sweeping revolution then, I hope, as treatments for the causes of aging become a reality, that will tear down the ridiculous systems of regulation that stifle development, with the result that effective therapies will become far less costly and far more widely available. A treatment that can address the causes of age-related disease is a treatment that should be undertaken by everyone on a regular basis, not just those who are heavily damaged by the processes of aging, and not just those groups that unaccountable bureaucrats decide should gain access. Today, the foundations for that future are still being built, one incremental step at a time, but is never too early to plan ahead.
When neurons die, their remains need to be eliminated quickly so that the surrounding brain tissue can continue functioning. A type of highly specialised cell known as microglia is responsible for this process which is called phagocytosis. Neurons are known to die during the convulsions associated with epilepsy. But contrary to expectations, in this condition the microglia are "blind" and incapable of either finding them or destroying them. Their behaviour is abnormal. And the dead neurons that cannot be eliminated build up and damage the neighbouring neurons further, which leads to an inflammatory response by the brain which harms and damages it even further. This discovery opens up a new channel for exploring therapies that could palliate the effects of brain diseases. In fact, the research group that authored this work is right now exploring the development of drugs to encourage this cleaning up process, phagocytosis.
The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.
Researchers have successfully reduced the symptoms and slowed the progression of Huntington's disease in mice using healthy human brain cells. The research entailed implanting the animals with human glia cells derived from stem cells. One of the roles of glia, an important support cell found in the brain, is to tend to the health of neurons and the study's findings show that replacing sick mouse glia with healthy human cells blunted the progress of the disease and rescued nerve cells at risk of death. Conversely, when healthy mice were implanted with human glia carrying the genetic mutation that causes Huntington's, the animals exhibited symptoms of the disease. The researchers believe that the healthy human glia were able to essentially stabilize and perhaps even rescue neurons by restoring the normal signaling function that is lost during the disease.
While strokes are known to increase risk for dementia, much less is known about diseases of large and small blood vessels in the brain, separate from stroke, and how they relate to dementia. Diseased blood vessels in the brain itself, which commonly is found in elderly people, may contribute more significantly to Alzheimer's disease dementia than was previously believed, according to new study results. The study analyzed medical and pathologic data on 1,143 older individuals who had donated their brains for research upon their deaths, including 478 (42 percent) with Alzheimer's disease dementia. Analyses of the brains showed that 445 (39 percent) of study participants had moderate to severe atherosclerosis - plaques in the larger arteries at the base of the brain obstructing blood flow - and 401 (35 percent) had brain arteriolosclerosis - in which there is stiffening or hardening of the smaller artery walls.
The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer's disease. The increase was 20 to 30 percent for each level of worsening severity. The study also found that atherosclerosis and arteriolosclerosis are associated with lower levels of thinking abilities, including in memory and other thinking skills, and these associations were present in persons with and without dementia.
The adult brain has some ability to adapt to changes in its environment. This ability is, in part, related to neurogenesis and gliogenesis. Neurogenesis modifies neuronal connectivity in specific brain areas, whereas gliogenesis ensures that myelination occurs and produces new supporting cells by generating oligodendrocytes and astrocytes. Altered neurogenesis and gliogenesis have been revealed in a number of pathological conditions affecting the central nervous system, indicating that modulation of the processes involved in adult neurogenesis and gliogenesis may provide a plausible strategy for treatment. Compared to neurogenesis, gliogenesis occurs more prevalently in the adult mammalian brain. Under certain circumstances, interaction occurs between neurogenesis and gliogenesis, facilitating glial cells to transform into neuronal lineage. Therefore, modulating the balance between neurogenesis and gliogenesis may present a new perspective for neurorestoration. These processes might be modulated toward functional repair of the adult brain.
Researchers have shown that the dopamine D2 receptor is linked to the long-term episodic memory, which function often reduces with age and due to dementia. This new insight can contribute to the understanding of why some but not others are affected by memory impairment. In this study, a PET camera was used to examine individual differences in the D2 system in a group consisting of 181 healthy individuals between the age of 64 and 68. All participants also had to take part in an all-inclusive performance test of the long-term episodic memory, working memory and processing speed along with an MRI assessment (which was used to measure the size of various parts of the brain). Researchers could see that the D2 system was positively linked to episodic memory, but not to working memory or to processing speed by relating PET registrations to the cognitive data. Researchers could also see that the D2 system affects the functioning of the hippocampus in the brain, long linked to long-term episodic memory.