Detects Abnormal Proteins In Spinal Fluid
The only way to definitively diagnose Alzheimer’s disease is with an autopsy, which doesn’t help the living. Most neurologists rely on the process of elimination and an educated guess. This guesswork makes case management challenging, while not improving the quality of life for patients. Those days could be numbered since researchers are finding simple and accurate ways to detect Alzheimer’s disease before people exhibit clinical symptoms.
According to researchers, neurologists can diagnose Alzheimer’s disease accurately by testing for peptides and proteins in a patient’s cerebrospinal fluids (CSF), which is collected with a lumbar puncture (spinal tap). Researchers can examine CSF for killer proteins—also known as beta-amyloid and tau. Tau tangles are thought to be toxic to neurons, and their spread through the brain foretells the death of brain tissue and cognitive decline. Tangles appear as the early, asymptomatic stage of Alzheimer’s develops into the symptomatic stage.
Researchers found that levels of a specific form of tau in the cerebrospinal fluid were elevated in the people with Alzheimer’s disease and that it increased as the disease progressed.
When tau spreads to neurons, patients experience confusion and memory loss. Most people don’t seek medical help until the disease reaches this point of dysfunction. Better diagnostics can improve disease management despite the lack of a cure.
The gold standard for measuring tau in the living brain is a tau-PET brain scan. Unfortunately, brain scans are expensive and not widely available. A spinal tap, also known as a lumbar puncture, is a more affordable way to determine whether a person has Alzheimer’s disease or a strong likelihood of developing the condition.
Cerebrospinal fluid, which has direct contact with the brain, offers a window into the brain’s condition.
Researchers have found that certain levels of tau and amyloid proteins in this fluid are associated with the disease, prompting many neurologists to include tests that look for these ‘biomarkers’ in cerebrospinal fluid in their diagnostic workup.
A test that measures amyloid and tau levels in cerebrospinal fluid can accurately identify most patients with Alzheimer’s disease, according to a study by Columbia University neurologists, and could play a wider role in diagnosing the disease.
A test that measures amyloid and tau levels in cerebrospinal fluid can accurately identify most patients with Alzheimer’s disease and could play a wider role in diagnosing the disease. Fortunately, the U.S. Food and Drug Administration just approved marketing for the first in vitro diagnostic test for early detection of amyloid plaques associated with Alzheimer’s disease. The Lumipulse G β-Amyloid Ratio test is intended for patients 55 years or older, who have cognitive impairment.
“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive PET scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” said Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health. “With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease.”
A lumbar puncture takes a sample of the cerebrospinal fluid from the lower spine.
This fluid flows around the spinal cord and the brain, and clears waste products. Levels of certain proteins in the cerebrospinal fluid reflect what is happening in the brain.
A special needle is used to take the sample of fluid from the lower back. Afterwards the person who had the sample taken is often asked to have a short rest. It is common for people to experience headaches or back pain after a lumbar puncture but these side effects usually settle over time. If people experience a headache after lumbar puncture, it typically starts 24-48 hours after the procedure.
In 2010, researchers reported that analyzing CSF can identify these abnormal proteins in all patients with significant memory loss who went on to develop Alzheimer’s disease. The researchers found that:
- Nearly every person with Alzheimer’s disease had abnormal proteins in their CSF;
- Almost 75 percent of those with mild cognitive impairment, which often precedes the onset of Alzheimer’s disease, had abnormal proteins in their CSF;
- One third of people with normal brain function had the biomarkers for the development of Alzheimer’s disease in the future; and
- All patients with mild cognitive impairment who developed Alzheimer’s disease within five years had the biomarkers five years prior.
In 2018, researchers combined three Alzheimer’s disease biomarkers in CSF – pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N), collectively called ATN. According to recent research from the Perelman School of Medicine at the University of Pennsylvania, the ATN framework also can detect frontotemporal dementia.
“Our study shows that this is a good test that can be used in clinical practice to reliably exclude other diagnoses in patients suspected of having Alzheimer’s disease,” says Richard Mayeux, MD, chair of the Department of Neurology at Columbia University Vagelos College of Physicians and Surgeons and senior author of the paper. “It’s better than amyloid PET scans, which only look at the amount of amyloid protein in the brain, because it measures amyloid and two types of tau protein.”
The test is performed with a lumbar puncture, a 30- to 40-minute procedure, performed with a local anesthetic, to collect the fluid. Fewer than 5 percent of patients experience a headache after this procedure.
“This test is much easier to administer and is much safer than many people think,” says Mayeux. “It also costs around $1,000 versus $3,500 for amyloid PET scan.”
A big issue: the coverage. Amyloid PET is not covered either. We have this FDA-approved procedure, but physicians are not ordering the test because it’s not covered by insurance. Hopefully, both CSF analysis and amyloid PET will be covered—they’re really great in improving diagnostic accuracy and influencing treatment decisions.
What should clinicians know about CSF analysis and the importance of an early and accurate diagnosis?
“We are noticing that patients are coming in earlier and earlier with their concerns,” said José Luis Molinuevo, M.D., Ph.D., Scientific Director of the Alzheimer Prevention Program at Barcelona Beta Brain Research Center in Spain. “Fifteen years ago, we were seeing people in the moderate stages of dementia. But now, we’re seeing more people with perceived cognitive decline, and these patients may be within normal range on their cognitive tests. Our task as clinicians and researchers is to find alternate, more accurate ways to detect the early biological signs of Alzheimer’s so we can answer as many of our patient’s questions as we can.”
Amyloid, Tau and Prion Disease
Dr. Stanley Prusiner, an American neuroscientist from the University of California at San Francisco, earned a Nobel Prize in 1997 for discovering and characterizing prions and prion disease. President Obama awarded Prusiner the National Medal of Science in 2010 to recognize the importance of his research. Important reforms to policies to protect public health, however, have been elusive. In 2019, Prusiner confirmed that Alzheimer’s disease is a prion disease—also known as transmissible spongiform encephalopathy (TSEs).
“This shows beyond a shadow of a doubt that amyloid beta and tau are both prions, and that Alzheimer’s disease is a double-prion disorder in which these two rogue proteins together destroy the brain,” said Stanley Prusiner, MD, the study’s senior author and director of the UCSF Institute for Neurodegenerative Diseases, part of the UCSF Weill Institute for Neurosciences. “The fact that prion levels also appear linked to patient longevity should change how we think about the way forward for developing treatments for the disease. We need a sea change in Alzheimer’s disease research, and that is what this paper does. This paper might catalyze a major change in AD research.”
Alzheimer’s disease is currently defined based on the presence of toxic protein aggregations in the brain known as amyloid plaques and tau tangles, accompanied by cognitive decline and dementia.
As mentioned above, TSEs are transmissible. Most hospitals, neurologists, surgeons, coroners and even morticians are aware of the prion threat. Unfortunately, family members and caregivers are not being warned. Since deadly prions spread through the bodily fluids and tissue of those carrying prion disease (milk, blood, saliva, mucus, urine, feces, tissue and skin), that seems to be a problem. Prions shed from infected humans are highly transmissible.
Prion disease has killed millions of people around the world over the past century. It’s impacting more people and more families than ever today. It’s also killing livestock, wildlife and sea mammals. The connection is undeniable. Wastewater mismanagement, industrial agriculture and modern medicine are fueling the flames of this public health disaster.
Alzheimer’s disease, Parkinson’s disease and Creutzfeldt-Jakob disease (CJD) are forms of prion disease.
Mad cow disease and chronic wasting disease also are forms of prion disease. Prion contamination from humans has infected wildlife and livestock. Prion contamination from wildlife and livestock has infected humans. It’s a vicious circle. Species barriers are a myth.
Prions are a deadly and unstoppable form of protein that migrates, mutates, multiplies and kills with unparalleled efficiency. Prions were first discovered in the late 1980s as a protein-containing biological agent that replicates itself in living cells without nucleic acid. Prions are not alive, which means that they can’t be killed. Neutralizing them is virtually impossible as they migrate, mutate and multiply. With each mutation, they become deadlier and more resistant.
Learn more about Dr. Stanley Prusiner and the Nobel Prize for prion science and prion disease.
Until recently, few have considered the possibility that Alzheimer’s disease is a transmissible disease. This denial and misinformation has been fueling a public health crisis around the world for years. Prion disease is highly contagious, incurable and fatal. Answers begin with the truth. Innocent victims are walking into prion pathways every day.
