Never-before-seen dna recombination in the brain linked to alzheimer’s disease sbp gas stations in texas

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Scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified gene recombination in neurons that produces thousands of new gene variants within Alzheimer’s disease brains. The study, published today in Nature, reveals for the first time how the Alzheimer’s-linked gene, APP, is recombined by using the same type of enzyme found in HIV.

Using new analytical methods focused on single and multiple-cell samples, the researchers found that the APP gene, which produces the toxic beta amyloid proteins defining Alzheimer’s disease, gives rise to novel gene variants in neurons—creating a genomic mosaic. The process required reverse transcription and reinsertion of the variants back into the original genome, producing permanent DNA sequence changes within the cell’s DNA blueprint.

“We used new approaches to study the APP gene, which gives rise to amyloid plaques, a pathological hallmark of the disease,” says Jerold Chun, M.D., Ph.D., senior author of the paper and professor and senior vice president of Neuroscience Drug Discovery at SBP. “Gene recombination was discovered as both a normal process for the brain and one that goes wrong in Alzheimer’s disease.”

One hundred percent of the Alzheimer’s disease brain samples contained an over-abundance of distinct APP gene variants, compared to samples from normal brains. Among these Alzheimer’s-enriched variations, the scientists identified 11 single-nucleotide changes identical to known mutations in familial Alzheimer’s disease—a very rare inherited form of the disorder. u gas cedar hill mo Although found in a mosaic pattern, the identical APP variants were observed in the most common form of Alzheimer’s disease, further linking gene recombination in neurons to disease.

“These findings may fundamentally change how we understand the brain and Alzheimer’s disease,” says Chun. “If we imagine DNA as a language that each cell uses to ‘speak,’ we found that in neurons, just a single word may produce many thousands of new, previously unrecognized words. This is a bit like a secret code embedded within our normal language that is decoded by gene recombination. The secret code is being used in healthy brains but also appears to be disrupted in Alzheimer’s disease.”

The scientists found that the gene recombination process required an enzyme called reverse transcriptase, the same type of enzyme HIV uses to infect cells. gas in chest Although there is no medical evidence that HIV or AIDS causes Alzheimer’s disease, existing FDA-approved antiretroviral therapies for HIV that block reverse transcriptase might also be able to halt the recombination process and could be explored as a new treatment for Alzheimer’s disease. The scientists noted the relative absence of proven Alzheimer’s disease in aging HIV patients on antiretroviral medication, supporting this possibility.

“The thousands of APP gene variations in Alzheimer’s disease provide a possible explanation for the failures of more than 400 clinical trials targeting single forms of beta-amyloid or involved enzymes,” says Chun. “APP gene recombination in Alzheimer’s disease may be producing many other genotoxic changes as well as disease-related proteins that were therapeutically missed in prior clinical trials. The functions of APP and beta-amyloid that are central to the amyloid hypothesis can now be re-evaluated in light of our gene recombination discovery.”

“Today’s discovery is a step forward—but there is so much that we still don’t know,” says Chun. “We hope to evaluate gene recombination in more brains, in different parts of the brain and involving other recombined genes—in Alzheimer’s disease as well as other neurodegenerative and neurological diseases—and use this knowledge to design effective therapies targeting gene recombination.”

He adds, “It is important to note that none of this work would have been possible without the altruistic generosity of brain donors and their loving families, to whom we are most grateful. Their generosity is yielding fundamental insights into the brain,and are leading us toward developing new and effective ways of treating Alzheimer’s disease and possibly other brain disorders—potentially helping millions of people. There is much more important work to be done.”

Alzheimer’s disease is a public health crisis. The cause of the disease remains unknown—and no meaningful treatment exists. electricity 1 unit how many watts Nearly six million people in the U.S. are living with Alzheimer’s disease, a number projected to reach 14 million by 2060 as the population ages. The annual health care system costs to care for people with the disease exceeds a quarter of a trillion dollars, according to the Alzheimer’s Association. The disease also places high burdens on family members: Caregivers of individuals with dementia report substantial emotional, financial and physical difficulties.

On average, it takes 10 years for a drug to receive FDA approval. This study provides scientific rationale for testing existing FDA approved antiretroviral drugs for HIV to evaluate effectiveness in AD patients. Studies could begin right away because these drugs have already undergone extensive safety testing and have been used safely for years to treat HIV.

In individuals with AD, neuronal recombination creates a myriad of APP gene variants, many of which are not observed in normal brains and may be pathological. gas density problems Creating gene variants requires an enzyme called reverse transcriptase, the same type of enzyme used by HIV to infect cells. There are a number of clinically safe, FDA-approved medicines used to treat HIV that block reverse transcriptase. These medicines can now be explored as a possible way to block the creation of pathological APP gene variants to treat AD in the very near future.

Cells of our immune system recombine DNA (called “VDJ recombination”)—which creates the diversity that allows the immune system to recognize a universe of unwanted intruders. Our sex cells, or gametes, also recombine DNA in a different way (called “homologous recombination”)—which creates the uniqueness of us. electricity words Our study shows for the first time that DNA recombination occurs in the brain.

Yes. In rare cases, neurodegenerative or neurological diseases such as autism, Parkinson’s disease, depression and schizophrenia are linked to gene mutations or amplifications—but the most common forms of these diseases seem to lack these links. Today’s findings support the possibility that gene recombination may underlie the most common forms of one or more of these disorders.

This study also provides an explanation for how the brain may normally store long-term memories, how it learns and how it changes (called “plasticity”), which is consistent with AD’s effects on memory. DNA, one of the most stable biological molecules in nature that can store information, could be used to retain long-term memories. Neuronal gene recombination could thus be a way to “record” as well as “play back” information, having normally beneficial but also pathologically detrimental effects.

There are a number of worthy organizations that accept brain donations. The National Institutes of Health NeuroBioBank ( neurobiobank.nih.gov/donors-how-become-donor) and your preferred university body donation programs (e.g., www.ucop.edu/ad-program) can assist you in the process. Your local chapter of the Alzheimer’s Association may also direct you to appropriate resources.