The Brain: Alzheimer's and dementia news and discussions

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Protocol predicts Alzheimer's 10 years in advance with 80% accuracy
By Michael Franco
April 12, 2023
https://newatlas.com/medical/glycans-pr ... lzheimers/

In seeking a safe yet effective way to predict Alzheimer's disease, researchers found a sugar molecule in the blood of affected patients. When combined with a simple memory test and genetic analysis, the research team was able to predict the onset of the condition up to a decade in advance with a significant degree of accuracy. The protocol could soon join others in helping scientists spot Alzheimer's in advance of its symptoms and take steps to halt its progression.

It seems that almost daily, scientists are getting closer and closer to finding new ways to predict the onset of Alzheimer's disease. We've seen attempts at using wearables to track movement patterns associated with the condition; algorithms that can analyze PET scans to spot signs of the disease years in advance; and analyses that have found 75 genomic regions associated with the disease. Testing of bodily fluids is also showing promise as a predictive modality but, because removing cerebrospinal fluid is always a risky proposition, researchers are trying to work out ways to spot the disease using much simpler blood tests.

That's the case for scientists at Karolinska Institutet (KI) in Sweden. Previously, researchers there showed that sugar-based substances called glycans found in cerebrospinal fluid could be linked to the presence of tau proteins in the body. High levels of abnormal tau in the brain is one of the primary markers of Alzheimer's disease, so finding it early in the body could be a way to predict the onset of the condition. In fact, the team found that people with matching levels of tau and glycans were twice as likely to develop Alzheimer's than those without the markers.
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Identifying 'hallmark' Parkinson's disease protein buildup could aid early detection, improved diagnosis and treatment
https://medicalxpress.com/news/2023-04- ... ildup.html
by Lancet
A technique that identifies the build-up of abnormal protein deposits linked to Parkinson's disease could aid in early detection and play a key role in the disease's clinical diagnosis and characterization, according to research published in The Lancet Neurology journal.

Findings from the study confirm that the technique—known as α-synuclein seed amplification assay (αSyn-SAA)—can accurately detect people with the neurodegenerative disease and suggest it can identify at-risk individuals and those with early, non-motor symptoms prior to diagnosis. The presence of misfolded α-synuclein protein aggregates in the brain is the pathological hallmark of Parkinson's disease.

Co-lead author Professor Andrew Siderowf, of the University of Pennsylvania Perelman School of Medicine (U.S.) and Parkinson Progression Marker Initiative (PPMI) investigator, says, "Recognizing heterogeneity in underlying pathology among patients with Parkinson's disease has been a major challenge. Identifying an effective biomarker for Parkinson's disease pathology could have profound implications for the way we treat the condition, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and speed up clinical trials."
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A new peptide may hold potential as an Alzheimer's treatment
https://medicalxpress.com/news/2023-04- ... tment.html
by Anne Trafton, Massachusetts Institute of Technology
MIT neuroscientists have found a way to reverse neurodegeneration and other symptoms of Alzheimer's disease by interfering with an enzyme that is typically overactive in the brains of Alzheimer's patients.

When the researchers treated mice with a peptide that blocks the hyperactive version of an enzyme called CDK5, they found dramatic reductions in neurodegeneration and DNA damage in the brain. These mice also showed improvements in their ability to perform tasks such as learning to navigate a water maze.

"We found that the effect of this peptide is just remarkable," says Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the senior author of the study. "We saw wonderful effects in terms of reducing neurodegeneration and neuroinflammatory responses, and even rescuing behavior deficits."
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Glucose-responsive, charge-switchable lipid nanoparticles for insulin delivery
https://phys.org/news/2023-04-glucose-r ... sulin.html
by Wiley
Patients with type 1 diabetes live with a constant risk of hyper- or hypoglycemia. Precisely controlled insulin release could help to improve regulation of their blood sugar levels. Reported in the journal Angewandte Chemie, a research team has now introduced a novel insulin formulation that can be switched on by glucose: Lipid nanoparticle carriers release more or less insulin depending on the blood sugar level.

Insulin levels in plasma are primarily regulated by β-cells in the pancreas and reflect fluctuations in the blood sugar level. Patients with type 1 diabetes can produce very little or no insulin and require several daily injections of a fast-acting insulin as well as one or two injections of a long-acting insulin to keep their blood sugar at a normal level.

Alternatively, they wear an insulin pump that provides continuous infusion. The insulin formulations cannot react to changes in the blood sugar level and thus do not allow for the precise regulation of blood sugar. If an insulin overdose is administered, a meal is missed, or too little carbohydrate consumed before strenuous physical activity, there is increased risk of acute, life-threatening hypoglycemia.

Insulin formulations that respond to glucose, mimicking the function of β-cells, could improve insulin therapy. Various approaches with insulin "carriers" made of polymers with incorporated glucose oxidase as a glucose detector suffer from two problems: The polymer carriers are not of uniform molecular weight and glucose oxidase is toxic if released into the body.
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In 'major breakthrough,' new test can detect Parkinson's disease before symptoms appear
A test of spinal fluid may be able to predict who is likely to develop Parkinson’s disease years before symptoms appear, according to a new study.

Parkinson’s is a degenerative syndrome that results in the gradual loss of brain circuitry involved in movement, thinking and behavior. It's the fastest-growing neurodegenerative condition in the U.S. and is diagnosed in about 90,000 Americans every year, according to a 2022 study.

There is no blood or laboratory testing that diagnoses Parkinson's disease, said Michael Henderson, a neuroscientist at the Van Andel Institute, a biomedical nonprofit dedicated to researching Parkinson's and other diseases.

But experts say this test using spinal fluid could be the first step toward less-invasive testing to diagnose Parkinson's disease using blood tests or nasal swabs.
https://www.msn.com/en-us/health/other/ ... r-AA19Rd5u
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Huge new study finds hearing aids may reduce dementia risk
By Paul McClure
April 13, 2023
https://newatlas.com/health-wellbeing/h ... ntia-risk/
Among older adults, hearing loss and dementia are both highly prevalent and are thought to be linked. In a huge new study, a team of international researchers has tried to determine how the two are linked.

It’s predicted that, by 2050, dementia will affect 150 million people worldwide. Hearing loss equal to or above 20 dB affects 10% of people aged 40 to 69, 30% of those over 65, and 70% to 90% of people aged 85 or older. For context, whispering heard from 5 ft (1.5 m) away produces a sound of 20 dB.

Studies have demonstrated a link between the two conditions, suggesting hearing loss is a modifiable risk factor for dementia. The 2020 Lancet Commission report on dementia prevention found that hearing loss might be linked to around 8% of worldwide dementia cases. As such, addressing hearing issues in older people, such as through the use of hearing aids, might be a way of reducing dementia risk.

A few studies have investigated the relationship between hearing aid use and dementia, but their findings have been inconsistent. A new study by a team of international researchers has examined the link between hearing aid use and dementia among middle-aged and older adults.
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Newfound link between Alzheimer's and iron could lead to new medical interventions
https://medicalxpress.com/news/2023-04- ... dical.html
by University of Texas at Austin
There is a growing body of evidence that iron in the brain may play a role in Alzheimer's disease. Lending weight to that idea, a new imaging probe has for the first time shown that in the same regions of the brain where the amyloid beta plaques associated with Alzheimer's occur, there is also an increase in iron redox, meaning the iron in these regions is more reactive in the presence of oxygen. Their imaging probe could yield even more details about the causes of Alzheimer's and help in the search for new drugs to treat it.

A team from The University of Texas at Austin and the University of Illinois at Urbana-Champaign has published a study today on the new imaging technique and findings in Science Advances.

"The link between iron redox and Alzheimer's disease has been a black box," said Yi Lu, corresponding author and professor of chemistry at UT Austin. "The most exciting part to me is that we now have a way to shine light into this black box so that we can begin to understand this whole process in much more detail."
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Alzheimer's proteins beaten back by sleeping pill in small study
By Michael Franco
April 20, 2023
https://newatlas.com/medical/alzheimers ... ping-pill/
Thirty-eight people took part in a study to investigate the effects of a sleep medication on Alzheimer's-related proteins in their cerebrospinal fluid. The pills showed promise in combating the substances that lead to the harmful tangles and plaques in the brain that contribute to the disease, but larger more comprehensive studies are needed to confirm the results.

It's been known that there's a bit of a Catch-22 involved when it comes to sleep and Alzheimer's disease. Poor sleep patterns have been linked to the development of the condition and, once someone has Alzheimer's disease, their sleep can be disrupted even many years before the symptoms of cognitive decline appear. Both sides of this coin are related to the build up of tau and amyloid beta, proteins that form plaques and tangles in the brain that harm neurons and lead to the development of Alzheimer's.

Interested in finding out if sleep medication might be a possible way to mitigate the effect of sleeplessness on the development of Alzheimer's disease, researchers at Washington University School of Medicine divided 38 study participants into three groups and conducted a two-night sleep study. The first group, the control, took no medication. The second group took a low dose of suvorexant (10 mg), an insomnia medication that blocks orexin, a molecule in the body that naturally keeps us awake. The third group took a higher dose of suvorexant (20 mg).
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Interfering with antiviral pathway may deter Alzheimer's disease and frontotemporal dementia
https://medicalxpress.com/news/2023-04- ... eimer.html
by Weill Cornell Medical College
Targeting part of an antiviral pathway triggered by the accumulation of a key pathogen shared in Alzheimer's disease and frontotemporal dementia may one day offer a new therapeutic approach to deterring or delaying cognitive decline, according to preclinical research led by Weill Cornell Medicine scientists.

The study, published April 24 in Nature Neuroscience, demonstrates that inhibiting an innate immune system enzyme called cyclic GMP-AMP synthase (cGAS) helps neurons become resilient to the build-up of the protein tau into bundles known as fibrils, a hallmark of Alzheimer's and some forms of frontotemporal dementia, the two most common dementias in the elderly population.

"We are interested in this antiviral pathway because of its importance in modulating innate immunity—the body's first line of defense against pathogens—which emerges as a major driver in neurodegenerative dementia," said the study's senior author, Dr. Li Gan, director of the Helen and Robert Appel Alzheimer's Disease Research Institute and the Burton P. and the Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases at Weill Cornell Medicine.
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First ‘gene silencing’ drug for Alzheimer’s disease shows promise
https://www.ucl.ac.uk/news/2023/apr/fir ... ws-promise
25 April 2023
A world-first trial at UCL and UCLH has found a new genetic therapy for Alzheimer’s disease that is able to safely and successfully lower levels of the harmful tau protein known to cause the disease.
tau protein

The trial, led by consultant neurologist Dr Catherine Mummery (UCL Queen Square Institute of Neurology & the National Hospital for Neurology and Neurosurgery), represents the first time that a ‘gene silencing’ approach has been taken in dementia and Alzheimer’s disease.

The approach uses a drug called BIIB080 (/IONIS-MAPTRx), which is an antisense oligonucleaotide (used to stop RNA producing a protein), to ‘silence’ the gene coding for the tau protein – known as the microtubule-associated protein tau (MAPT) gene. This prevents the gene from being translated into the protein in a doseable and reversible way. It will also lower the production of that protein and alter the course of disease.
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