PET scans
Getting Closer to a Blood Test for Alzheimer’s Disease?
Posted on by Dr. Francis Collins
As research on Alzheimer’s disease (AD) advances, a desperate need remains for an easy blood test to help diagnose the condition as early as possible. Ideally, such a test could also distinguish AD from other forms of dementia that produce similar symptoms. As published recently in Nature Medicine, an NIH-funded research team has designed a simple blood test that is on course to meet these criteria [1].
The latest work builds on a large body of work showing that one secret to predicting a person’s cognitive decline and treatment response in AD lies in a protein called tau. Using the powerful, but expensive, approach of PET scan imaging, we know that tau builds up in the brain as Alzheimer’s disease progresses. We also know that some tau spills from the brain into the bloodstream.
The trouble is that the circulating tau protein breaks down far too quickly for a blood test to offer a reliable measure of what’s happening in a person’s brain. A few years ago, researchers discovered a possible solution: test for blood levels of a slightly different and more stable version of the protein called pTau181 [2]. (The “p” in its name comes from the addition of phosphorus in a particular part of the protein’s structure.)
In the latest study, researchers in the lab of Adam Boxer, University of California, San Francisco, followed up further on this compelling lead. Boxer’s team measured pTau181 levels in blood samples from 362 people between the ages of 58 and 70. Those samples included 56 people with an Alzheimer’s diagnosis, along with 47 people with mild cognitive impairment and 69 healthy controls.
The researchers also included another 190 people diagnosed with frontotemporal lobar degeneration (FTLD). It is a relatively rare form of dementia that leads to a gradual decline in behavior, language, and movement, often in connection with a buildup of tau in the brain.
The study found that levels of pTau181 were roughly 3.5-times higher in the blood of people with AD compared to people without AD. Those with mild cognitive impairment due to underlying AD also showed an intermediate increase in blood levels of pTau181.
Importantly, people with FLTD had normal blood levels of pTau181. As a result, the blood test could reliably distinguish between a person with AD and a person with FLTD. That’s important because, while FLTD is a relatively rare condition, its prevalence is similar to AD in people under the age of 65. But both conditions have similar symptoms, making it often challenging to distinguish them.
The findings add to evidence that the new blood test can help in diagnosing AD and in distinguishing it from other neurodegenerative conditions. In fact, it does so with an accuracy that often rivals more expensive PET scans and more invasive cerebrospinal fluid tests, which are now the only reliable ways to measure tau.
There’s still plenty of work to do before this blood test is ready for a doctor’s office. But these initial findings are very promising in helping to simplify the diagnosis of this devastating condition that now affects an estimated 5.5 million Americans [3].
References:
[1] Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L, Bourakova V, Cobigo Y, Heuer H, Spina S, VandeVrede L, Chai X, Proctor NK, Airey DC, Shcherbinin S, Duggan Evans C, Sims JR, Zetterberg H, Blennow K, Karydas AM, Teunissen CE, Kramer JH, Grinberg LT, Seeley WW, Rosen H, Boeve BF, Miller BL, Rabinovici GD, Dage JL, Rojas JC, Boxer AL; Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) investigators. Nat Med. 2020 Mar 2.
[2] Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, Airey DC, Knopman DS, Roberts RO, Machulda MM, Jack CR Jr, Petersen RC, Dage JL. Alzheimers Dement. 2018 Aug;14(8):989-997.
[3] Alzheimer’s Disease Fact Sheet. National Institute on Aging, May 22, 2019.
Links:
Alzheimer’s Disease & Related Dementias (National Institute on Aging/NIH)
What Are Frontotemporal Disorders? (NIA)
Accelerating Medicines Partnership: Alzheimer’s Disease (NIH)
Adam Boxer (University of California, San Francisco)
NIH Support: National Institute on Aging; National Institute of Neurological Disorders and Stroke; National Center for Advancing Translational Sciences
Alzheimer’s Disease: Tau Protein Predicts Early Memory Loss
Posted on by Dr. Francis Collins
Caption: PET scan images show distribution of tau (top panel) and beta-amyloid (bottom panel) across a brain with early Alzheimer’s disease. Red indicates highest levels of protein binding, dark blue the lowest, yellows and oranges indicate moderate binding.
Credit: Brier et al., Sci Transl Med
In people with Alzheimer’s disease, changes in the brain begin many years before the first sign of memory problems. Those changes include the gradual accumulation of beta-amyloid peptides and tau proteins, which form plaques and tangles that are considered hallmarks of the disease. While amyloid plaques have received much attention as an early indicator of disease, until very recently there hadn’t been any way during life to measure the buildup of tau protein in the brain. As a result, much less is known about the timing and distribution of tau tangles and its relationship to memory loss.
Now, in a study published in Science Translational Medicine, an NIH-supported research team has produced some of the first maps showing where tau proteins build up in the brains of people with early Alzheimer’s disease [1]. The new findings suggest that while beta-amyloid remains a reliable early sign of Alzheimer’s disease, tau may be a more informative predictor of a person’s cognitive decline and potential response to treatment.
Imaging Willpower: Using Brain Scans to Explore Obesity
Posted on by Dr. Francis Collins
For some people, the smell of Mom’s home-baked pie, the sight of an ice cream truck, or the sound of sizzling French fries can trigger a feeding frenzy. But others find it much easier to resist such temptations. What’s the explanation?
You might think it’s sheer willpower. But a recent study in the journal Molecular Psychiatry suggests the answer to what fuels susceptibility to food cues may be far more complex, related to subtle differences in brain chemistry [1].
