Breakthrough research provides early detection of Alzheimer’s disease
[June 21, 2023: Staff Writer, The Brighter Side of News]
Mass General Brigham, a premier healthcare system, has unearthed a remarkable revelation regarding the early detection of Alzheimer's disease. (CREDIT: Creative Commons)
In the earliest stages of Alzheimer’s disease, before the outward symptoms of cognitive decline have emerged, sufferers' intestines harbor a distinctively different mix of bacteria compared to those found in the guts of healthy individuals. This significant discovery, revealed in a recent study by scientists at the Washington University School of Medicine in St. Louis, might pave the way for innovative methods of early detection and intervention to prevent the onset of dementia.
The study, published in Science Translational Medicine, has brought to light the tantalizing possibility of using the gut bacterial community analysis as a tool to identify people at higher risk of developing Alzheimer’s disease. Moreover, the findings also point towards the potential of microbiome-altering preventive treatments as a means of warding off cognitive decline.
“The crux of our investigation lies in understanding the complex interplay between the gut and the brain, and its impact on Alzheimer’s progression. While we are yet to establish whether the gut influences the brain or vice versa, the value of this association is undeniable,” stated Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine and co-corresponding author of the study.
In highlighting the implications of their findings, Dr. Dantas proposed two alternative interpretations. “The shift in the gut microbiome may be a mere readout of pathological changes occurring in the brain. On the other hand, it’s also possible that the gut microbiome actively contributes to the development of Alzheimer’s disease. If the latter holds true, intervention strategies such as probiotics or fecal transfers, targeting the gut microbiome, may offer a promising avenue for altering the course of the disease,” he conjectured.
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This pivotal study germinated from an innocuous conversation between Dr. Dantas and his colleague Beau M. Ances, MD, PhD, the Daniel J. Brennan Professor of Neurology, during their children's soccer game. While Dr. Ances specializes in treating and studying Alzheimer's disease, Dr. Dantas is a renowned expert in the field of gut microbiome. They converged on the novel idea of examining the link between the gut microbiome and Alzheimer's disease.
Previous scientific research had already revealed distinct differences between the gut microbiomes of healthy individuals and those with symptomatic Alzheimer's disease. However, as Dr. Ances pointed out to Dr. Dantas, no one had yet ventured to examine the gut microbiomes of individuals during the crucial pre-symptomatic phase of the disease.
Dr. Ances, the other co-corresponding author of the study, said, “Significant, often irreversible changes occur in the brain by the time cognitive symptoms begin to manifest. Therefore, an early diagnosis, at the onset of these changes, would be the most effective time to intervene with a therapy.”
Healthy and preclinical AD individuals have distinct gut microbiome profiles. Stacked taxonomic (MetaPhlAn3) bar plots at the genus level stratified by preclinical AD status are shown, with color grouping at the phylum level. u, unclassified. (CREDIT: Science Translational Medicine)
During the early phase of Alzheimer's disease, which can span over two decades, individuals begin to accumulate clumps of proteins known as amyloid beta and tau in their brains. Despite these abnormal protein accumulations, they do not yet display any signs of neurodegeneration or cognitive decline.
The team, which included first author Aura L. Ferreiro, PhD, a former graduate student in Dr. Dantas' lab and now a postdoctoral researcher, evaluated participants who volunteer for studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University. Each participant was cognitively normal at the start of the study. They provided stool, blood, and cerebrospinal fluid samples; maintained food diaries; and underwent PET and MRI brain scans as part of the research.
Pairwise Spearman correlations between microbiome summary metrics (green) and AD biomarkers (blue, Aβ; purple, tau; orange, neurodegeneration; brown, vascular injury; gray, genetic risk factors). Significant correlations are shown (P < 0.05, Benjamini-Hochberg adjusted), with the size of the circle inversely proportional to the P value. Inset values are Spearman correlations. WMH, white matter hyperintensities. (CREDIT: Science Translational Medicine)
The team identified participants already in the early stage of Alzheimer's disease from those who were healthy by looking for signs of amyloid beta and tau accumulation through brain scans and cerebrospinal fluid. Out of the 164 participants, about a third (49) showed signs of early Alzheimer's.
The analysis unveiled stark differences between the gut bacteria of healthy individuals and those with preclinical Alzheimer's disease. The differences were noted both in terms of the species of bacteria present and the biological processes they were involved in. Interestingly, these differences bore no correlation to the participants' diet, which remained largely the same.
These bacterial differences correlated with the levels of amyloid and tau proteins, which elevate before cognitive symptoms manifest, but did not correlate with neurodegeneration. Neurodegeneration becomes evident approximately at the same time when cognitive skills start to decline. The researchers suggested these differences could potentially be used as a screening tool for early Alzheimer's disease.
Linear regressions of AD biomarkers against gut microbiome–derived axes. Specifically, regressions of PET Aβ, PET tau, or cortical thickness (a measure of neurodegeneration) against PCoA sample coordinates derived from MetaPhlan3 taxonomic profiles (top and middle rows) or HUMAnN 3.0 functional pathway profiles (bottom row) (CREDIT: Science Translational Medicine)
“The beauty of using the gut microbiome as a screening tool lies in its simplicity and ease,” expressed Dr. Ances. “It’s not far-fetched to imagine a future where individuals can simply provide a stool sample to find out if they are at increased risk for developing Alzheimer's disease. This method would be far easier, less invasive, and more accessible for a large proportion of the population, especially for underrepresented groups, compared to brain scans or spinal taps.”
In their quest to decipher whether the differences in the gut microbiome are a cause or a result of the brain changes seen in early Alzheimer's disease, the researchers have embarked on a five-year follow-up study.
“If a causative link is established, it is highly likely to be inflammatory in nature,” speculated Dr. Dantas, who also holds professorships in pathology & immunology, biomedical engineering, molecular microbiology, and pediatrics. “Bacteria are remarkable biochemical factories, producing metabolites that can influence inflammation in the gut or even seep into the bloodstream, where they can affect the immune system throughout the body. While these are just hypotheses at this stage, if proven correct, they could guide us towards strategies that promote 'good' bacteria or eliminate 'bad' bacteria. Such microbiome-targeted interventions could potentially slow down or even halt the development of symptomatic Alzheimer's disease.”
Who has Alzheimer’s Disease?
In 2020, as many as 5.8 million Americans were living with Alzheimer’s disease.
Younger people may get Alzheimer’s disease, but it is less common.
The number of people living with the disease doubles every 5 years beyond age 65.
This number is projected to nearly triple to 14 million people by 2060.
Symptoms of the disease can first appear after age 60, and the risk increases with age.
What is known about Alzheimer’s Disease?
Scientists do not yet fully understand what causes Alzheimer’s disease. There likely is not a single cause but rather several factors that can affect each person differently.
Age is the best known risk factor for Alzheimer’s disease.
Family history—researchers believe that genetics may play a role in developing Alzheimer’s disease. However, genes do not equal destiny. A healthy lifestyle may help reduce your risk of developing Alzheimer’s disease. Two large, long term studies indicate that adequate physical activity, a nutritious diet, limited alcohol consumption, and not smoking may help people.
Changes in the brain can begin years before the first symptoms appear.
Researchers are studying whether education, diet, and environment play a role in developing Alzheimer’s disease.
There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline.
What is the burden of Alzheimer’s disease in the United States?
Alzheimer’s disease is one of the top 10 leading causes of death in the United States.
The 6th leading cause of death among US adults.
The 5th leading cause of death among adults aged 65 years or older.
In 2020, an estimated 5.8 million Americans aged 65 years or older had Alzheimer’s disease. This number is projected to nearly triple to 14 million people by 2060.
In 2010, the costs of treating Alzheimer’s disease were projected to fall between $159 and $215 billion. By 2040, these costs are projected to jump to between $379 and more than $500 billion annually.
Death rates for Alzheimer’s disease are increasing, unlike heart disease and cancer death rates that are on the decline.
Dementia, including Alzheimer’s disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimer’s may be considerably higher.
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