Study points to possible treatments and confirms distinction between memory loss due to aging and that of Alzheimer’s
A team of Columbia University Medical Center (CUMC) researchers, led by Nobel laureate Eric R. Kandel, MD, has found that deficiency of a protein called RbAp48 in the hippocampus is a significant contributor to age-related memory loss and that this form of memory loss is reversible. The study, conducted in postmortem human brain cells and in mice, also offers the strongest causal evidence that age-related memory loss and Alzheimer’s disease are distinct conditions. The findings were published today in the online edition of Science Translational Medicine.
“Our study provides compelling evidence that age-related memory loss is a syndrome in its own right, apart from Alzheimer’s. In addition to the implications for the study, diagnosis, and treatment of memory disorders, these results have public health consequences,” said Dr. Kandel, who is University Professor & Kavli Professor of Brain Science, co-director of Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, director of the Kavli Institute for Brain Science, and senior investigator, Howard Hughes Medical Institute, at CUMC. Dr. Kandel received a share of the 2000 Nobel Prize in Physiology or Medicine for his discoveries related to the molecular basis of memory.
The hippocampus, a brain region that consists of several interconnected subregions, each with a distinct neuron population, plays a vital role in memory. Studies have shown that Alzheimer’s disease hampers memory by first acting on the entorhinal cortex (EC), a brain region that provides the major input pathways to the hippocampus. It was initially thought that age-related memory loss is an early manifestation of Alzheimer’s, but mounting evidence suggests that it is a distinct process that affects the dentate gyrus (DG), a subregion of the hippocampus that receives direct input from the EC.
“Until now, however, no one has been able to identify specific molecular defects involved in age-related memory loss in humans,” said co-senior author Scott A. Small, MD, the Boris and Rose Katz Professor of Neurology and director of the Alzheimer’s Research Center at CUMC.
The current study was designed to look for more direct evidence that age-related memory loss differs from Alzheimer’s disease. The researchers began by performing microarray (gene expression) analyses of postmortem brain cells from the DG of eight people, ages 33 to 88, all of whom were free of brain disease. The team also analyzed cells from their EC, which served as controls since that brain structure is unaffected by aging. The analyses identified 17 candidate genes that might be related to aging in the DG. The most significant changes occurred in a gene called RbAp48, whose expression declined steadily with aging across the study subjects.
To determine whether RbAp48 plays an active role in age-related memory loss, the researchers turned to mouse studies. “The first question was whether RbAp48 is downregulated in aged mice,” said lead author Elias Pavlopoulos, PhD, associate research scientist in neuroscience at CUMC. “And indeed, that turned out to be the case—there was a reduction of RbAp48 protein in the DG.”
When the researchers genetically inhibited RbAp48 in the brains of healthy young mice, they found the same memory loss as in aged mice, as measured by novel object recognition and water maze memory tests. When RbAp48 inhibition was turned off, the mice’s memory returned to normal.
The researchers also did functional MRI (fMRI) studies of the mice with inhibited RbAp48 and found a selective effect in the DG, similar to that seen in fMRI studies of aged mice, monkeys, and humans. This effect of RbAp48 inhibition on the DG was accompanied by defects in molecular mechanisms similar to those found in aged mice. The fMRI profile and mechanistic defects of the mice with inhibited RbAp48 returned to normal when the inhibition was turned off.
In another experiment, the researchers used viral gene transfer and increased RbAp48expression in the DG of aged mice. “We were astonished that not only did this improve the mice’s performance on the memory tests, but their performance was comparable to that of young mice,” said Dr. Pavlopoulos.
“The fact that we were able to reverse age-related memory loss in mice is very encouraging,” said Dr. Kandel. “Of course, it’s possible that other changes in the DG contribute to this form of memory loss. But at the very least, it shows that this protein is a major factor, and it speaks to the fact that age-related memory loss is due to a functional change in neurons of some sort. Unlike with Alzheimer’s, there is no significant loss of neurons.”
The Latest Bing News on:
Age-Related Memory Loss
- Secrets of ‘superagers’on April 30, 2024 at 12:32 pm
Those folks are called “superagers.” And researchers have been trying for a long time to figure out what causes them to be special and the degree to which it might be genetic versus action based. The ...
- Loneliness increases as we age, study suggestson April 30, 2024 at 8:00 am
Loneliness increases as we age, study suggests - The study found that people with higher persistent loneliness were disproportionately women, had a lower income and were less educated.
- Neuroscientists find integrity of white brain matter in superagers does not deteriorate, explains sharp memoryon April 30, 2024 at 7:40 am
A team of neuroscientists from Universidad Politécnica de Madrid and Queen Sofia Foundation Alzheimer Center, both in Spain, has found that so-called superagers maintain memory as they grow older ...
- “I Lost 130 lbs at Age 53!” — Here's the Protein Combo That Builds Muscle + Boosts Weight Losson April 29, 2024 at 10:58 am
Dr. Lyon recommends aiming for 30–50 grams at each meal, with special emphasis on the first meal of the day, when we tend to get the least protein. Bonus: Lots of morning protein and protein ...
- Neuroscientists Reveal Secret of Superagers' Excellent Memorieson April 29, 2024 at 10:00 am
White matter, which connects different regions of the brain, appears to retain better structure in superagers than in older people with memory decline.
- Misplaced your keys? How to distinguish dementia from normal age-related memory losson April 29, 2024 at 2:17 am
Experts say misplacing keys or other everyday items isn't necessarily a sign of dementia or other serious memory loss issues. They note there are ways you can keep your memory sharp.
- The #1 Spice for Better Brain Health, Recommended by Dietitianson April 26, 2024 at 1:02 pm
Drumroll…Turmeric is our number one spice for brain health. A spice native to Southeast Asia and primarily grown in India, turmeric has long been studied for its health benefits, helping with ...
- This Is What Your Poop Schedule Says About Your Risk of Cognitive Declineon April 25, 2024 at 10:04 pm
Constipation may be connected to worsening cognitive function, new research finds. The studies were of over 100,000 people.
- Researchers Find Evidence That Brains Are Getting Biggeron April 25, 2024 at 1:04 pm
“Larger brain structures like those observed in our study may reflect improved brain development and improved brain health,” DeCarli explained. “A larger brain structure represents a larger brain ...
- Recognizing the signs: When a loved one needs memory supporton April 22, 2024 at 4:04 am
Struggling to perform once routine tasks can be a warning sign that a loved one is experiencing memory loss. The Mayo Clinic advises that difficulty with tasks an older adult has performed for years, ...
The Latest Google Headlines on:
Age-Related Memory Loss
[google_news title=”” keyword=”Age-Related Memory Loss” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
The Latest Bing News on:
Memory loss
- The Loss of a Pet Can Be Heartbreaking — Here's How to Help Someone Going Through Iton April 30, 2024 at 10:12 am
About 70% of U.S. households own a pet, according to the 2021-2022 National Pet Owners Survey conducted by the American Pet Products Association (APPA). So, many of us have experienced firsthand the ...
- Discover Expert-Approved Hacks To Combat Memory Declineon April 30, 2024 at 9:13 am
Once serious memory loss takes hold, treatment options tend to be limited and uncertain. Here are some hacks that may help with memory loss.
- Samsung's operating profit soars 930% as AI tailwinds drive demand for memory chipson April 30, 2024 at 9:04 am
Samsung Electronics said on Tuesday that its operating profit surged more than 930% in the first quarter of 2024, driven by soaring demand for its servers, memory chips and storage used in AI ...
- Neuroscientists find integrity of white brain matter in superagers does not deteriorate, explains sharp memoryon April 30, 2024 at 7:40 am
A team of neuroscientists from Universidad Politécnica de Madrid and Queen Sofia Foundation Alzheimer Center, both in Spain, has found that so-called superagers maintain memory as they grow older ...
- 'Tragic loss': Charlotte officials mourn four law enforcement officialson April 30, 2024 at 6:07 am
Flowers in memory of fallen law enforcement officers accumulate at the base of a flag pole outside the Federal Courthouse on April 30, 2024 in Charlotte, North Carolina. (Sean Rayford/Getty Images) ...
- Samsung sees memory biz return to profit, upbeat about foundry saleson April 30, 2024 at 1:36 am
Samsung Electronics has reported operating profits of KRW6.61 trillion (US$4.78 billion) on consolidated revenue of KRW71.92 trillion for the first quarter of 2024. Revenue was primarily driven by ...
- Urgent Search for Missing 74-Year-Old Man with Memory Loss in Pembroke Pineson April 29, 2024 at 5:31 pm
Pembroke Pines Police search for missing 74-year-old Wilfredo Brito, who has memory loss and was last seen driving a gold Toyota Corolla.
- Palestinians mourn loss of culture with the rising death toll amid ongoing Israel-Hamas waron April 29, 2024 at 9:05 am
The massive loss of life in the Israel-Hamas war has wiped out swaths of family lines -- and gone with them are parts of the culture they carried, Palestinians say.
- Misplaced your keys? How to distinguish dementia from normal age-related memory losson April 29, 2024 at 2:17 am
Experts say misplacing keys or other everyday items isn't necessarily a sign of dementia or other serious memory loss issues. They note there are ways you can keep your memory sharp.
- Memory café launches to combat lonelinesson April 28, 2024 at 10:19 pm
A new memory cafe has opened in the grounds of what is thought to be the largest stately home in the UK. Based in the newly restored Camelia House at Wentworth Woodhouse, the Home Instead Memory Café ...
The Latest Google Headlines on:
Memory loss
[google_news title=”” keyword=”memory loss” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]