Skin cells from volunteers with Down's syndrome have been turned into brain cells in order to provide a new model for researchers to study Alzheimer's disease.
People with Down's syndrome are at high risk of developing Alzheimer's disease and show the first signs of the disease around 40 years earlier than those in the general population. To try and understand why this is, Cambridge University, where this research took place, has also launched a separate £1 million brain imaging study.
In the current study, published in , researchers used a two-step process to turn volunteers' skin cells into brain cells with Alzheimer's disease. The skin cells were first transformed into induced pluripotent stem (iPS) cells, which can be made to turn into almost any cell type in the body. Here, the iPS cells were turned into nerve cells which behaved identically to cells in the human brain.
After being grown for a short period of time in the lab, the newly-created cells showed all the characteristics of brain cells taken from Alzheimer's disease patients post-mortem. It is hoped that the cells will therefore provide an easier way for researchers to study how the disease starts and progresses.
Alzheimer's disease can take years or even decades to develop. As Dr Rick Livesey, who led the current study, said: 'One of the biggest challenges facing dementia researchers at the moment is a lack of good ways to track the disease over time. By using stem cells donated from people with Down's syndrome, we have been able to track how the disease develops over a shorter time period than has been possible in the past'.
….although Down Syndrome is a DNA mutation, I believe that Alzheimer's is caused by environmental poisoning. What is the link?
Prion diseases are unique transmissible neurodegenerative diseases that have diverse phenotypes and can be familial, sporadic, or acquired by infection. …
Roger Reeves: Mouse models of epigenetics
Dr. Reeves studies specific changes in the craniofacial skeleton that are largely responsible for the characteristic facial appearance in Down syndrome and contribute to sleep apnea and other clinical presentations. The Reeves laboratory has traced these changes to the cells of origin, the neural crest. He is helping the Feinberg lab test its stochastic epigenetic plasticity model in mice, and he is working with Dr. Reddy on nuclear structure in Down syndrome.
EPIGENETICS AND INHERITANCE
We used to think that a new embryo's epigenome was completely erased and rebuilt from scratch. But this isn't completely true. Some epigenetic tags remain in place as genetic information passes from generation to generation, a process called epigenetic inheritance.
Epigenetic inheritance is an unconventional finding. It goes against the idea that inheritance happens only through the DNA code that passes from parent to offspring. It means that a parent's experiences, in the form of epigenetic tags, can be passed down to future generations.
As unconventional as it may be, there is little doubt that epigenetic inheritance is real. In fact, it explains some strange patterns of inheritance geneticists have been puzzling over for decades.
Epigenetic Influences and Disease
The external environment's effects upon genes can influence disease, and some of these effects can be inherited in humans. …
What Is Epigenetics? How Do Epigenetic Changes Affect Genes?
Epigenetics involves genetic control by factors other than an individual's DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed.
Epigenetics is involved in many normal cellular processes. Consider the fact that our cells all have the same DNA, but our bodies contain many different types of cells: neurons, liver cells, pancreatic cells, inflammatory cells, and others. How can this be? In short, cells, tissues, and organs differ because they have certain sets of genes that are "turned on" or expressed, as well as other sets that are "turned off" or inhibited. Epigenetic silencing is one way to turn genes off, and it can contribute to differential expression. Silencing might also explain, in part, why genetic twins are not phenotypically identical. In addition, epigenetics is important for X-chromosome inactivation in female mammals, which is necessary so that females do not have twice the number of X-chromosome gene products as males (Egger et al., 2004). Thus, the significance of turning genes off via epigenetic changes is readily apparent.
Within cells, there are three systems that can interact with each other to silence genes: DNA methylation, histone modifications, and RNA-associated silencing…
A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease
….Although most cases of Alzheimer's disease are sporadic, kindreds with autosomal-dominant inheritance of the syndrome suggest that a single mutation may be important in pathogenesis. Direct sequencing of DNA from a family with autopsy-proven Alzheimer's disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and may be the inherited factor causing both amyloid fibril formation and dementia.
What Is the Role of Genetics in Familial Alzheimer's Disease?
Alzheimer's disease strikes early and fairly often in certain families, often enough to be singled out as a separate form of the disease and given a label: early-onset familial Alzheimer's disease, or FAD. Combing through the DNA of these families, researchers have found an abnormality in one gene on chromosome 21 that is common to a few of the families. And they have linked a much larger proportion of early-onset families to recently identified and related genes on chromosomes 1 and 14.
The chromosome 21 gene also intrigues Alzheimer's researchers because of its role in Down syndrome. People with Down syndrome have an extra copy of chromosome 21 and, as they grow older, usually develop abnormalities in the brain like those found in Alzheimer's disease.
Few researchers think that the search for Alzheimer's genes is over. Most investigators are convinced that there are many more genes involved in Alzheimer's disease and, moreover, that other conditions must also be present for the disease to develop. One of these conditions may be a problem with the way in which nerves turn sugar, or glucose, into energy, a process known as glucose metabolism.
Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type
An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. ...