Daily Archives: January 14, 2014

Jan. 14, 2014 The presence of a gene variant in people with mild cognitive impairment (MCI) is associated with accelerated rates of brain atrophy, according to a new study published online in the journal Radiology.

The study focused on the gene apolipoprotein E (APOE), the most important genetic factor known in non-familial Alzheimer's disease (AD). APOE has different alleles, or gene variations, said the study's senior author, Jeffrey R. Petrella, M.D., associate professor of radiology at Duke University School of Medicine in Durham, N.C.

"We all carry two APOE alleles, and most people have at least one copy of the APOE epsilon 3 (3) variant, which is considered neutral with respect to Alzheimer's risk," Dr. Petrella said.

The less common epsilon 4 (4) allele, in contrast, is associated with a higher risk for development of AD, earlier age of onset, and faster progression in those affected, as compared with the other APOE alleles.

Dr. Petrella and colleagues recently analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) involving 237 patients, mean age 79.9, with MCI, a slight but noticeable decline in cognitive ability that is tied to a higher risk of AD. The researchers used MRI to measure brain atrophy rates in these patients over a 12- to 48-month period.

The 4 carriers in the study group exhibited markedly greater atrophy rates than 3 carriers in 13 of 15 brain regions hypothesized to be key components of the cognitive networks disrupted in AD.

"The results showed atrophy in brain regions we know are affected by AD, in a population of patients who do not have AD, but are at risk for it," Dr. Petrella said. "This suggests the possibility of a genotype-specific network of related brain regions that undergo faster atrophy in MCI and potentially underlies the observed cognitive decline."

The researchers did not explore why APOE 4 might accelerate atrophy, but the affect is likely due to a combination of factors, noted Dr. Petrella.

"The protein has a broad role in the transport and normal metabolism of lipids and a protective function on behalf of brain cells, including its role in the breakdown of beta-amyloid, one of the proteins implicated in the pathophysiology of AD," he said.

With MRI playing an increasingly prominent role in MCI research, Dr. Petrella predicted that increased knowledge about the effects of APOE will improve the design and execution of future clinical trials. For instance, researchers could enrich their samples with 4 patients in MCI prevention trials to better determine potential treatment effects on brain regions vulnerable to degeneration.

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Gene variation associated with brain atrophy in mild cognitive impairment

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Newswise While the ability of human embryonic stem cells (hESCs) to become any type of mature cell, from neuron to heart to skin and bone, is indisputably crucial to human development, no less important is the mechanism needed to maintain hESCs in their pluripotent state until such change is required.

In a paper published in this weeks Online Early Edition of PNAS, researchers from the University of California, San Diego School of Medicine identify a key gene receptor and signaling pathway essential to doing just that maintaining hESCs in an undifferentiated state.

The finding sheds new light upon the fundamental biology of hESCs with their huge potential as a diverse therapeutic tool but also suggests a new target for attacking cancer stem cells, which likely rely upon the same receptor and pathway to help spur their rampant, unwanted growth.

The research, led by principal investigator Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, focuses upon the role of the highly conserved WNT signaling pathway, a large family of genes long recognized as a critical regulator of stem cell self-renewal, and a particular encoded receptor known as frizzled family receptor 7 or FZD7.

WNT signaling through FZD7 is necessary to maintain hESCs in an undifferentiated state, said Willert. If we block FZD7 function, thus interfering with the WNT pathway, hESCs exit their undifferentiated and pluripotent state.

The researchers proved this by using an antibody-like protein that binds to FZD7, hindering its function. Once FZD7 function is blocked with this FZD7-specific compound, hESCs are no longer able to receive the WNT signal essential to maintaining their undifferentiated state.

FZD7 is a so-called onco-fetal protein, expressed only during embryonic development and by certain human tumors. Other studies have suggested that FZD7 may be a marker for cancer stem cells and play an important role in promoting tumor growth. If so, said Willert, disrupting FZD7 function in cancer cells is likely to interfere with their development and growth just as it does in hESCs.

Willert and colleagues, including co-author Dennis Carson, MD, of the Sanford Consortium for Regenerative Medicine and professor emeritus at UC San Diego, plan to further test their FZD7-blocking compound as a potential cancer treatment.

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Keeping Stem Cells Pluripotent

Oak Brook, Ill. (PRWEB) January 13, 2014

The presence of a gene variant in people with mild cognitive impairment (MCI) is associated with accelerated rates of brain atrophy, according to a new study published online in the journal Radiology.

The study focused on the gene apolipoprotein E (APOE), the most important genetic factor known in non-familial Alzheimers disease (AD). APOE has different alleles, or gene variations, said the studys senior author, Jeffrey R. Petrella, M.D., associate professor of radiology at Duke University School of Medicine in Durham, N.C.

We all carry two APOE alleles, and most people have at least one copy of the APOE epsilon 3 (3) variant, which is considered neutral with respect to Alzheimers risk, Dr. Petrella said.

The less common epsilon 4 (4) allele, in contrast, is associated with a higher risk for development of AD, earlier age of onset, and faster progression in those affected, as compared with the other APOE alleles.

Dr. Petrella and colleagues recently analyzed data from the Alzheimers Disease Neuroimaging Initiative (ADNI) involving 237 patients, mean age 79.9, with MCI, a slight but noticeable decline in cognitive ability that is tied to a higher risk of AD. The researchers used MRI to measure brain atrophy rates in these patients over a 12- to 48-month period.

The 4 carriers in the study group exhibited markedly greater atrophy rates than 3 carriers in 13 of 15 brain regions hypothesized to be key components of the cognitive networks disrupted in AD.

The results showed atrophy in brain regions we know are affected by AD, in a population of patients who do not have AD, but are at risk for it, Dr. Petrella said. This suggests the possibility of a genotype-specific network of related brain regions that undergo faster atrophy in MCI and potentially underlies the observed cognitive decline.

The researchers did not explore why APOE 4 might accelerate atrophy, but the affect is likely due to a combination of factors, noted Dr. Petrella.

The protein has a broad role in the transport and normal metabolism of lipids and a protective function on behalf of brain cells, including its role in the breakdown of beta-amyloid, one of the proteins implicated in the pathophysiology of AD, he said.

See original here:
RSNA: Gene Variation Associated with Brain Atrophy in Mild Cognitive Impairment