Research Roundup: Big Focus on Alzheimer’s Disease and More
Every week there are numerous scientific studies published. This week there was an unusual number of research stories revolving around Alzheimer’s disease. Here’s a look at some of the more interesting ones.
Simple Blood Test for Early Detection of Alzheimer’s
Investigators at Hong Kong University of Science and Technology developed a simple blood test for early detection and screening of Alzheimer’s disease. It has an accuracy of more than 96%. The team identified 19 out of the 429 plasma proteins associated with Alzheimer’s to form a biomarker panel that provides an AD signature in the blood. They then developed a scoring system that could differentiate AD patients from healthy people, and also differentiate among the early, intermediate, and late stages of the disease. They published their research in the journal Alzheimer’s & Dementia.
“With the advancement of ultrasensitive blood-based protein detection technology, we have developed a simple, non-invasive, and accurate diagnostic solution for AD, which will greatly facilitate population-scale screening and staging of the disease,” said Nancy Ip, Morningside Professor of Life Science and the director of the State Key Laboratory of Molecular Neuroscience at HKUST.
The research was conducted with the University College London and local hospitals including the Prince of Wales Hospital and Queen Elizabeth Hospital. It utilized the proximity extension assay (PEA) to study the levels of more than 1,000 proteins in the plasma of AD patients in Hong Kong.
Reversing Dementia in Mice
Investigators at Tohoku University identified a potential therapeutic that not only seems to halt neurodegenerative symptoms in laboratory animals, but seems to reverse the effects of the diseases, specifically dementia and Alzheimer’s disease. They published their research in the International Journal of Molecular Sciences, and the Japanese regulatory board has declared the drug safe, and the researchers expect to begin human clinical trials next year. In earlier research, the research team found that the SAK3 molecule seemed to improve memory and learning in a mouse model of Alzheimer’s disease. SAK3 seems to enhance the function of a cell membrane channel, further promoting neuronal activity in the brain. The same drug, SAK3, also seemed to work in a mouse model of Lewy body dementia. And even after onset of cognition problems, the drug seemed to significantly prevent the progression of neurodegenerative behaviors in motor dysfunction and cognition. One of the key theories of Alzheimer’s is that it is caused or exacerbated by the accumulation of amyloid plaques. The recently approved Biogen drug Aduhelm is a monoclonal antibody that clears beta-amyloid. The researchers note that SAK3 inhibits the accumulation of misfolded alpha-synuclein, which is associated with neurodegenerative disorders, but also, at least in mice, also destroys amyloid plaque.
New Alzheimer’s Database in Diverse Populations Now Available
The University of North Texas Health Science Center has made available a database with data that came out of the Health and Aging Brain among Latino Elders (HABLE) study that was launched in 2017. The data includes the biology of Alzheimer’s among Mexican Americans as well as non-Hispanic whites within the context of sociocultural, environmental and behavioral factors. One of the early findings is that beta-amyloid, one of the biomarkers of Alzheimer’s, is less common among Mexican Americans yet this population appears to have a younger onset of cognitive loss. Approximately 1,000 Mexican Americans and 1,000 non-Latino whites over 50 from North Texas have enrolled in the study. The data accumulated include reoccurring and free comprehensive interviews, functional exams, clinical lab tests, a brain MRI and PET scans.
Key Tau Switch that Triggers Protein Accumulation in Alzheimer’s IDed
Researchers at the Tokyo Metropolitan University have identified a specific feature of the tau protein that causes it to accumulate in the brain and trigger Alzheimer’s and other tau-related illnesses. Disulfide bonds on specific amino acids stabilize tau and cause it to accumulate, which gets worse with increased oxidative stress. Normally, tau helps form and stabilize microtubules, the filaments that crisscross the inside of cells and help keep them structurally rigid. But when they don’t form correctly, they accumulate in sticky clumps. These clumps in the brain block the firing of neurons, involved in a wide range of neurodegenerative diseases called tauopathies, of which Alzheimer’s is one. They published their research in Human Molecular Genetics.
Saturated Fatty Acid Levels Rise as Memories are Made
Researchers at the University of Queensland found that saturated fatty acid levels rise in the brain during the formation of memories. They were testing the most common fatty acids, which were viewed as important to health and memory, but were surprised to find that the changes of saturated fat levels in the brain cells were most pronounced when new memories were formed. In particular, the most marked was myristic acid, found in coconut oil and butter. Fatty acids are the building blocks of lipids or fats and are important for communication between nerve cells. The highest concentration of saturated fatty acids was in the amygdala, the part of the brain that forms new memories specifically related to fear and strong emotions.
Maybe it’s Not Amyloid Plaques in Alzheimer’s, but Amyloid-Beta Peptide
Even with Biogen’s approval of aducanumab to remove amyloid plaques in Alzheimer’s patients’ brains, the amyloid theory is being debated. A study out of the University of Cincinnati theorizes that amyloid plaques—hardened clumps of beta-amyloid—may be a consequence of Alzheimer’s, but not the cause of the memory and cognition issues. In their research, they found that cognitive impairment appeared to be due to a drop in soluble amyloid-beta peptide instead of the accumulation of amyloid plaques. They analyzed the brain scans and spinal fluid from 600 people enrolled in the Alzheimer’s Disease Neuroimaging Initiative study, who all had amyloid plaques. They compared the amount of plaques and levels of the peptide in the people with normal cognition to those with cognitive impairment. They found that the individuals with high levels of the peptide were cognitively normal, regardless of the amount of brain plaques. They also found higher levels of the peptide were associated with a larger hippocampus, the area of the brain associated with memory.
“It’s not the plaques that are causing impaired cognition,” says Alberto Espay, the study’s senior author and professor of neurology at UC. “Amyloid plaques are a consequence, not a cause.” He went on to say that future approaches will look at replenishing these brain soluble proteins to normal levels.