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Sep 19, 2020

A Diet High in Salt May Promote Cognitive Impairment

A new study from Drs. Iadecola and Faraco published in Nature offers new insights into why and how skipping the salt-shaker might protect your cognitive health. The National Institute of Health has long advised that high-salt diets are associated with high blood pressure and can raise the risk for heart disease, stroke, kidney failure, and can cause immune-related changes in the gut. This most recent study suggests that high salt intake can also impact cognitive function by causing a deficiency in a compound – nitric oxide – that is crucial for maintaining vascular health in the brain and that new findings tie to tau, one of the hallmark Alzheimer’s proteins.

A study in 2018 from the same team found that a high-salt diet contributed to cognitive deficits in mice. The mice in this study had memory impairment and were unable to complete the tasks of daily living such as building their nests. The conclusion from this earlier study was that the high-salt diet caused cells in the small intestine to release a molecule known as interleukin-17 (IL-17) which promotes inflammation as part of the body’s immune response. IL-17 enters the bloodstream where it prevented cells in the walls of the blood vessels from providing the brain with nitric oxide. Nitric oxide is crucial for relaxing and widening the blood vessels to allow blood to flow; a shortage of nitric oxide can restrict blood flow.

Following up on these initial findings, the study recently published in Nature takes the research a step farther by investigating how a change in nitric oxide production in the blood vessels affects the stability of tau proteins in neurons.

In an interview about the research, Dr. Iadecola said: “tau becomes unstable by coming off the cytoskeleton. Tau is not supposed to be free in the cell. Once tau detaches from the cytoskeleton, the protein can accumulate in the brain, causing cognitive problems.” The research provides evidence for nitric oxide playing a role in keeping tau in check.

In a crucial experiment, the researchers gave mice eating a high-salt diet an antibody to promote tau stability. Despite restricted blood flow in these mice, the researchers observed that they had normal cognition. This experiment demonstrated that the cognitive deficits in the mice on the high-salt diet were due to the effect of tau rather than restricted blood flow alone.

This research paves the way to conduct research on how salt intake affects cognition in humans – specifically Alzheimer’s patients. CureAlz is actively supporting research investigating the links among dietary salt, cardiovascular function, tau deposition, and cognitive decline.


May 27, 2020

Proteins in the Blood may Predict Age

New research shows that measuring proteins in the blood may predict both health and lifespan. The research was published in Nature Medicine with support from a grant from Cure Alzheimer’s Fund. Tony Wyss-Coray, PH.D. and a team of scientists have used advances in protein profiling technology to measure thousands of proteins in the plasma at points across the human lifespan in order to determine what profiles are associated with healthy aging and with disease.

Blood has cells that transport oxygen, fight infectious disease, and carry messenger molecules with information across organ systems. The blood contains hormone-like factors that promote growth and survival; the composition of these factors changes during aging and with disease. The hormone-like factors involved in cell injury, repair, and inflammation increase during aging while those involved in the maintenance and development of tissue decrease with age. Blood tests are beginning to be used as a diagnostic and prognostic tool for many diseases including cancer, brain trauma, and heart failure, as well as amyloid plaque levels in the brain.

Using a technology called SOMAmer the researcher team measured the levels of nearly 3,000 different plasma proteins from more than 4,000 healthy individuals ages 18 – 95. As a key part of the study, the team identified 373 proteins in the blood that showed consistent changes with age across the lifespan of both mice and humans. Using machine learning techniques, this protein change data was used to train an artificial intelligence tool to predict biological age based on a sample donor’s protein profile.  In validation testing, the tool predicted a biological age that was younger than a person’s chronological age for individuals who were indeed healthier both cognitively and physically than individuals of the same chronological age but for whom the tool predicted a correct or older biological age.  The authors hope that this proteomic clock may someday be used to identify individuals at risk for disease.


Jan 29, 2020

ATXN1 Plays a role in learning and memory

CELL has published the results of a collaboration between Rudy Tanzi, PH.D. and Huda Zoghbi, M.D. The work shows that a rare gene associated with an increased risk of Alzheimer’s, ATXN1, regulates an increase in BACE1, an enzyme that contributes to amyloid plaque accumulation.

Neurodegenerative disorders tend to fall into two distinct categories that are not thought of as overlapping: those that affect movement, called ataxias, and those that affect mental functioning, called dementias. ATXN1 is a rare Alzheimer’s associated gene that has been extensively studied in spinocerebellar ataxia type1 (SCA1), a neurodegenerative disorder.  SCA1 has no known effective treatment or cure and can affect anyone at any age. In many cases, people are not aware that they carry a relevant gene until after they have children. An estimated 150,000 people are living with spinocerebellar ataxia in the United States and the average age of onset is in the forties. SCA1 symptomsvinclude the deterioration of motor coordination, balance, and progressive difficulty in swallowing and breathing in late stages. Impairments in verbal memory and frontal executive dysfunction also occur in later stages of the disease.

ATXN1 is a rare Alzheimer’s associated gene that has been studied in the neurodegenerative disorder, spinocerebellar ataxia type 1. Those who suffer from this disorder experience Alzheimer’s like dementia later in the progression of the disease. To test the hypothesis that ATXN1 might be involved in Alzheimer’s disease, the researchers used mice that were genetically modified to have the ATXN1 gene knocked out. The researchers were interested in determining whether the loss of ATXN1 would lead to biochemical changes that resembled the changes observed in the brain during Alzheimer’s disease. BACE1, the b-secretase enzyme that cleaves amyloid precursor protein and generates amyloid plaques, was increased by 45% in the ATXN1 knockout mice. These mice display impairments in learning in the hippocampus. This paper provides evidence that ATXN1 plays a role in learning and memory.

Prior to this study, there has been no evidence that any known candidate genes for Alzheimer’s disease could regulate BACE1 expression in the brain.

This paper is groundbreaking for its ability to demonstrate a unique regulatory mechanism by which ATXN1, a gene more commonly associated with motor neurodegeneration, can affect BACE1 levels. An increase in BACE1 expression can decrease neural precursor cell proliferation and negatively impact learning, memory, and the birth of new neurons. An interesting next direction for the field will be to determine how altering levels of amyloid precursor protein or BACE1 influences adult hippocampal neurogenesis – a process that is known to go awry in Alzheimer’s.


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