New Study Reveals Blood Proteins That Predict Disease-Causing Aging Cells

 How will your competent? doctor use this to slow down your biological aging? Doing nothing, like usual!

New Study Reveals Blood Proteins That Predict Disease-Causing Aging Cells

Blood protein structure changes may enable earlier detection of Alzheimer’s

Your competent? doctor figured out what to do about proteostasis years ago, right.

• proteostasis (4 posts to March 2023)

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Blood protein structure changes may enable earlier detection of Alzheimer’s

A recent study in Nature Aging combined mass spectrometry-based structural proteomics with machine learning to establish a minimally invasive, reliable, and potentially scalable research strategy for early detection and classification of Alzheimer’s disease (AD) and related cognitive conditions.

Protein homeostasis disruption and structural biomarkers in Alzheimer’s disease

Proteostasis, or protein homeostasis, refers to the cellular processes that maintain proper protein folding, stability, and degradation. These mechanisms are crucial because a substantial proportion of newly synthesized proteins can misfold, disrupting normal cell function if not managed by cellular quality control systems.

In AD, the machinery responsible for proteostasis becomes less effective, allowing misfolded proteins and damaged cellular components to build up over time. This impaired clearance supports the early accumulation of amyloid-β aggregates, abnormal protein clumps that can form in the brain years before the first signs of Alzheimer’s symptoms appear. A comprehensive understanding of protein conformational changes and interactions, beyond the traditional focus on amyloid plaques and tau tangles, could uncover disease mechanisms and plasma-based structural biomarkers.

Apolipoprotein E (APOE) is a polymorphic plasma protein with three major isoforms (ε2, ε3, ε4) differing by one or two amino acids, leading to altered binding properties. The ε4 allele is strongly associated with increased AD risk, while ε2 confers protection. Despite extensive characterization of APOE genotype expression profiles and network effects, the impact of APOE variants on the structure of ApoE-interacting proteins remains underexplored.

Neuropsychiatric symptoms (NPSs) are prevalent in AD, with sex differences noted in progression and symptomatology. Women tend to experience more rapid cognitive decline and higher rates of delusion, while men exhibit increased apathy and agitation. Despite growing efforts to define molecular correlates of NPSs, the relationship between sex and NPSs remains unclear due to clinical heterogeneity in AD.

Assessing protein structure alterations in Alzheimer’s disease

Blood samples were collected from participants at the University of California, San Diego (UCSD) and the University of Southern California Alzheimer’s Disease Research Centers. Alzheimer’s pathology in the UCSD cohort was supported by cerebrospinal fluid (CSF) measurements of amyloid-β and tau, while clinical status across cohorts was evaluated using established diagnostic criteria. Participants were assessed biannually for cognitive function and categorized using standard criteria, including the Clinical Dementia Rating (CDR) and neuropsychological testing.

Peptide samples were analyzed by Liquid Chromatography–Tandem Mass Spectrometry (LC–MS/MS) coupled to a timsTOF Pro mass spectrometer. A machine learning framework was used to classify mass spectrometry data, with a deep neural network selected after benchmarking against 17 additional machine learning algorithms.

Identification of structural blood biomarkers for early AD detection

A total of 520 blood samples were obtained from two large cohorts. By combining blood assessment findings with detailed clinical and biomarker data, including cognitive tests and cerebrospinal fluid (CSF) measures, where available, researchers classified Alzheimer’s disease (AD) status and progression.

Tracking organ aging and disease

 If you want to become a super-ager you'll want your doctor to be closely following this.  If you know about this before your doctor does, you don't have a functioning stroke doctor!

Tracking organ aging and disease

At a Glance

• Researchers found that proteins in the blood can be used to track the aging of individual organs, and that faster organ aging increased the risk of disease and death.
• The technique could be used to predict a person’s risk for certain diseases and develop more targeted interventions.

Researchers were able to determine the biological ages of different organs, along with the risk for associated diseases, by examining blood proteins. Ground Picture / Shutterstock

Different people age at different rates. Two people of the same age may show dramatically different signs of aging. Scientists developed the concept of biological age to account for this variation. Biological age can be estimated based on various biomarkers. Research in animals has found that different organs in the same organism can also age at different rates. But it’s not clear if this is true in humans, or whether organ aging affects the risk of disease.

An NIH-funded research team, led by Dr. Tony Wyss-Coray at Stanford University, sought to develop a way to track the aging of various organs in the human body. To do so, they analyzed gene activity in different organs and measured levels of almost 5,000 proteins in blood plasma from more than 5,600 people across the adult lifespan. The results appeared in Nature on December 6, 2023.

Using gene activity data, the team first determined that almost 900 of the proteins were enriched in a single organ. They then trained machine learning models to estimate biological age using blood plasma levels of these proteins at different ages. Models were trained for 11 organs: fat tissue, arteries, brain, heart, immune tissue, intestines, kidneys, liver, lungs, muscle, and pancreas.

The team found that almost 20% of people showed accelerated aging in a single organ. Fewer than 2% had accelerated aging in more than one organ. When the researchers examined data on nine age-related diseases, they found that many of the diseases were associated with faster aging in particular organs. For example, people with hypertension and diabetes had “older” kidneys than their same-aged peers. Older hearts were associated with atrial fibrillation and heart attacks. People with accelerated heart aging had more than double the risk of heart failure over the next 15 years. For most organs, accelerated aging led to a 15-50% greater risk of death from any cause.

The approach gave insights into brain aging, too. A protein called pTau-181 is an established blood-based biomarker for Alzheimer’s disease. The researchers found that proteins associated with brain aging could predict Alzheimer’s progression as well as pTau-181. High levels of both brain aging and pTau-181 were associated with greater risk than a high level of one or the other alone.

In addition, proteins associated with artery aging predicted the onset of mild cognitive impairment. These proteins implicate certain molecular processes in early cognitive decline. Identifying the molecular processes underlying disease could lead to new strategies to prevent or treat them.

“We can estimate the biological age of an organ in an apparently healthy person,” Wyss-Coray explains. “That, in turn, predicts a person’s risk for disease related to that organ.”

He notes that the technique will need to be tested on many more people before it can be used in the clinic. If it holds up, it could allow providers to treat people who are at risk before they get sick.

—by Brian Doctrow, Ph.D.

Protein in blood may predict prognosis, recovery from stroke

Who the fuck cares that you are predicting failure to recover, certainly not survivors. If my doctor would have honestly predicted my failure to recover I would have screamed in his face about his complete failure in doing his job. But he punted and told me nothing, no protocols, no guidelines; ABSOLUTELY NOTHING. And the reason he told me nothing was because he knew nothing as proven by his writing 3 prescriptions to OT, PT, ST of E.T.(Evaluate and Treat)

Protein in blood may predict prognosis, recovery from stroke

Researchers at Mayo Clinic in Florida and collaborators have found that a biomarker in the blood may determine the extent of brain injury from different types of strokes and predict prognosis in these patients. Their findings are reported in Science Translational Medicine.

The blood biomarker is a protein known as neurofilament light (NFL). The protein is abundant in neurons found in the brain. When neurons are injured following a stroke or from other neurological diseases, NFL is released into cerebrospinal fluid that bathes the brain and then into the blood. The amount of NFL released is indicative of neuron injury in the brain, according to the research team. Stroke is a leading cause of death, but symptoms vary widely from temporary and nondisabling, to severe, long-term impairment.

"Estimating the severity of a stroke and how well a person is expected to recover is important to patients and their loved ones," says Tania Gendron, Ph.D., first author of the paper.

"Reliably predicting a patient's prognosis is also important to their care, as it informs treatment and rehabilitation decisions. We sought to determine whether the amount of NFL in patients' blood could be used to predict their prognosis after a stroke—be it an ischemic stroke, which occurs when blood flow to the brain is blocked by a clot, or a hemorrhagic stroke, which occurs when a weak blood vessel bursts and bleeds into the brain."

The retrospective study involved participants who enrolled in, and donated blood for, the Mayo Clinic in Florida Familial Cerebrovascular Diseases Registry directed by James Meschia, M.D., a neurologist and chair of the Department of Neurology at Mayo Clinic in Florida. Researchers used an investigative blood test to measure NFL concentrations in blood collected from 314 patients following a stroke and in blood from 79 healthy individuals. This allowed them to determine whether NFL is elevated after a stroke. They also examined whether NFL levels are indicative of stroke severity and eventual recovery. To do so, the researchers examined correlations between NFL levels and the degree of brain injury, in addition to neurological, functional or cognitive status of patients at the time their blood was collected. The study also examined whether NFL levels could anticipate future recovery by reliably predicting post-stroke outcomes and survival. To verify their findings, the researchers used a similar approach to evaluate NFL as a prognostic biomarker in two additional groups of stroke patients.

The blood samples and clinical information were provided by clinical research authors on the paper from Mayo Clinic, University of Pennsylvania, Yale University, Massachusetts General Hospital and Washington University.

"We discovered that blood levels of NFL do predict stroke severity," says Leonard Petrucelli, Ph.D., one of the senior authors on the paper. "We found that higher NFL levels forecast worse functional outcomes and shorter survival time after a stroke. We found this to be the case for ischemic stroke and hemorrhagic strokes. Our study establishes NFL as a promising prognostic biomarker for stroke." Dr. Petrucelli is the Ralph B. and Ruth K. Abrams Professor of Neuroscience.

Currently, brain imaging is used to determine damage from a stroke. While a blood test for NFL is not yet available in the clinical setting, researchers hope that in the future, physicians may be able to decrease use of imaging—using instead an NFL blood test to better determine the best course of treatment—as well as boost clinical trials with better matched groups of patients based on degree of brain injury and severity of symptoms.

"We are hopeful that our findings will ultimately change how patients are treated by using NFL biomarkers in clinical trials to allow for more rapid and reliable detection of therapeutic effects," says Dr. Meschia. "Our findings may also help us better plan rehabilitation needs for patients who need it most and for longer term."

 

Aging Research: Blood Proteins Show Your Age

Your doctor needs to take these results and come up with protocols that reduce your age. Along with the protocols that recover your 5 lost cognitive years from your stroke. 

This is all your doctor's responsibility, don't let them weasel out of it.

Aging Research: Blood Proteins Show Your Age

How can you tell how old someone is? Of course, you could scan their driver’s license or look for signs of facial wrinkles and gray hair. But, as researchers just found in a new study, you also could get pretty close to the answer by doing a blood test.
That may seem surprising. But in a recent study in Nature Medicine, an NIH-funded research team was able to gauge a person’s age quite reliably by analyzing a blood sample for levels of a few hundred proteins. The results offer important new insights into what happens as we age. For example, the team suggests that the biological aging process isn’t steady and appears to accelerate periodically—with the greatest bursts coming, on average, around ages 34, 60, and 78.
These findings indicate that it may be possible one day to devise a blood test to identify individuals who are aging faster biologically than others. Such folks might be at risk earlier in life for cardiovascular problems, Alzheimer’s disease, osteoarthritis, and other age-related health issues.
What’s more, this work raises hope for interventions that may slow down the “proteomic clock” and perhaps help to keep people biologically younger than their chronological age. Such a scenario might sound like pure fantasy, but this same group of researchers showed a few years ago that it’s indeed possible to rejuvenate an older mouse by infusing blood from a much younger mouse.
Those and other earlier findings from the lab of Tony Wyss-Coray, Stanford School of Medicine, Palo Alto, CA, raised the tantalizing possibility that certain substances in young blood can revitalize the aging brain and other parts of the body. In search of additional clues in the new study, the Wyss-Coray team tracked how the protein composition of blood changes as people age.
To find those clues, they isolated plasma from more than 4,200 healthy individuals between ages 18 and 95. The researchers then used data from more than half of the participants to assemble a “proteomic clock” of aging.  Within certain limits, the clock could accurately predict the chronological age of the study’s remaining 1,446 participants. The best predictions relied on just 373 of the clock’s almost 3,000 proteins.
As further validation, the clock also reliably predicted the correct chronological age of four groups of people not in the study. Interestingly, it was possible to make a decent age prediction based on just nine of the clock’s most informative proteins.
The findings show that telltale proteomic changes arise with age, and they likely have important and as-yet unknown health implications. After all, those proteins found circulating in the bloodstream come not just from blood cells but also from cells throughout the body. Intriguingly, the researchers report that people who appeared biologically younger than their actual chronological age based on their blood proteins also performed better on cognitive and physical tests.
Most of us view aging as a gradual, linear process. However, the protein evidence suggests that, biologically, aging follows a more complex pattern. Some proteins did gradually tick up or down over time in an almost linear fashion. But the levels of many other proteins rose or fell more markedly over time. For instance, one neural protein in the blood stayed constant until around age 60, when its levels spiked. Why that is so remains to be determined.
As noted, the researchers found evidence that the aging process includes a series of three bursts. Wyss-Coray said he found it especially interesting that the first burst happens in early mid-life, around age 34, well before common signs of aging and its associated health problems would manifest.
It’s also well known that men and women age differently, and this study adds to that evidence. About two-thirds of the proteins that changed with age also differed between the sexes. However, because the effect of aging on the most important proteins of the clock is much stronger than the differences in gender, the proteomic clock still could accurately predict the ages in all people.
Overall, the findings show that protein substances in blood can serve as a useful measure of a person’s chronological and biological age and—together with Wyss-Coray’s earlier studies—that substances in blood may play an active role in the aging process. Wyss-Coray reports that his team continues to dig deeper into its data, hoping to learn more about the origins of particular proteins in the bloodstream, what they mean for our health, and how to potentially turn back the proteomic clock.
Reference:
[1] Undulating changes in human plasma proteome profiles across the lifespan. Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, Moran Losada P, Berdnik D, Keller A, Verghese J, Sathyan S, Franceschi C, Milman S, Barzilai N, Wyss-Coray T. Nat Med. 2019 Dec;25(12):1843-1850.

New Blood Test Can Rapidly Diagnose Brain Injuries - 10 minutes

How can this be repurposed to diagnose stroke? 

New Blood Test Can Rapidly Diagnose Brain Injuries - 10 minutes

A new blood testing device could help reduce the time and expenses needed to diagnose brain injuries.
A team— which includes researchers from the University of Geneva (UNIGE) and hospitals in Barcelona, Madrid and Seville—has developed a small device that by analyzing the level of certain proteins in the blood can indicate the possibility of a mild traumatic brain injury using just a single droplet of blood.
"We wondered if it was possible to isolate certain proteins whose presence in the blood increases in the event of mild traumatic brain injury," Jean-Charles Sanchez, professor at the Department of Internal Medicine of Specialties and the Biomarkers Centre of the Faculty of Medicine of the UNIGE, said in a statement. "Our idea was to find a way to do a quick examination that would allow, during a boxing or American football match for example, to determine whether the athlete can return to the field or if his condition requires hospitalization. The opposite of the CT Scan, an exam that lasts a long time and cannot be done anywhere."
Head injuries can cause various symptoms, including blurred vision, vomiting, and the loss of consciousness or memory for following the event. There is then a risk of mild cerebral trauma, which represent more than 90 percent of the brain injuries admitted to hospitals, and often requires expensive CT Scans to diagnose the injury.
During a shock to the head, some brain cells are damaged and release proteins that increase their level in the blood. The researchers were able to compare the blood of patients admitted for mild traumatic brain injuries that were diagnosed as negative with that of patients suffering from a brain lesion.
They then used proteomic analysis to quantify thousands of proteins simultaneously and observe variations in their levels in the blood, and gradually isolated four molecules—H-FABP, Interleukin-10, S100B and GFAP—to indicate the presence of a brain injury.
The point of care test, dubbed TBIcheck, uses a single drop of blood on the well of a small five-centimeter plastic case and alerts the patient within 10 minutes whether there is a risk of mild trauma—particularly whether the H-FABP level is 2.5 nanograms per milliliter of blood.
"We have noticed that the H-FABP level alone makes it possible to confirm that there is no risk of trauma in one third of patients admitted after a shock," Jean-Charles Sanchez said in a statement. “The rest of the patients will have to undergo a CT scan to confirm the diagnosis.”
A Cube Reader that will display positive or negative on the screen and send the result to a smartphone could also be installed.
The researchers next plan to refine the testing device, with the goal of developing a test capable of diagnosing brain trauma, strokes and aneurysms.
"Today, our research shows that the results are even more accurate when we combine H-FABP and GFAP levels," Jean-Charles Sanchez said. "We are currently preparing an even more effective TBIcheck, which will allow 50% of patients to be sent home, but which requires an increase in the sensitivity of the test that receives the blood. Biomarkers are a mine of information on patients' state of health, it is up to us to decode them."
The study was published in PLOS One.