News | PET Imaging | May 12, 2016

Brain Imaging Links Alzheimer’s Decline to Tau Protein

New PET imaging agent reveals tau is better marker of progression to Alzheimer’s disease than amyloid beta

tau protein, Alzheimer's, PET scan, imaging agent, brain decline, Washington University in St. Louis

A study using a new PET imaging agent shows that measures of tau protein in the brain more closely track cognitive decline due to Alzheimer's disease compared with long-studied measures of amyloid beta. More red color indicates more tau protein. The image on the left shows the average tau accumulation in the brains of cognitively normal people, averaged over many individuals. The image on the right shows the average amount of tau buildup in the brains of multiple people with mild Alzheimer's symptoms. Scanning multiple individuals shows that the intensity of tau deposits correlates with the severity of cognitive dysfunction. Image courtesy of Matthew R. Brier.

May 12, 2016 — A buildup of plaque and dysfunctional proteins in the brain are hallmarks of Alzheimer’s disease. While much Alzheimer’s research has focused on accumulation of the protein amyloid beta, researchers have begun to pay closer attention to another protein, tau, long associated with this disease but not studied as thoroughly, in part, because scientists only recently have developed effective ways to image tau.

Using a new imaging agent that binds to tau protein and makes it visible in positron emission tomography (PET) scans, scientists at Washington University School of Medicine in St. Louis have shown that measures of tau are better markers of the cognitive decline characteristic of Alzheimer’s than measures of amyloid beta seen in PET scans.

The new study is published May 11 in the journal Science Translational Medicine.

Comparing brain images of people who are cognitively normal to patients with mild Alzheimer’s disease, the researchers found that measures of tau better predict symptoms of dementia than measures of amyloid beta. To determine degrees of cognitive impairment, some of the participants who underwent brain imaging also were assessed with the traditional clinical dementia rating (CDR) scale, cerebrospinal fluid measures, and widely used pen and paper tests of memory and other brain functions.

“Our work and that of others has shown that elevated levels of amyloid beta are the earliest markers of developing Alzheimer’s disease,” said senior author Beau M. Ances, M.D., Ph.D., an associate professor of neurology. “But in the earliest stages of Alzheimer’s disease, even with amyloid buildup, many patients are cognitively normal, meaning their memory and thought processes are still intact. What we suspect is that amyloid changes first and then tau, and it’s the combination of both that tips the patient from being asymptomatic to showing mild cognitive impairment.”

The study included 36 control participants who were cognitively normal and 10 patients with mild Alzheimer’s disease. While Ances called for larger follow-up studies, he said this analysis helped establish that the new tau agent, called T807, is an important tool for understanding the timeline of Alzheimer’s progression and for defining which regions of the brain are involved.

“Usually we can only diagnose patients later in the disease process, when brain function already is diminished,” he said. “We want to develop ways to make an earlier diagnosis and then design trials to test drugs against amyloid buildup and against tau buildup. While we currently cannot prevent or cure Alzheimer’s disease, delaying the onset of symptoms by 10-15 years would make a huge difference to our patients, to their families and caregivers, and to the global economy.”

Beyond establishing a timeline, Ances said the new tool is vital to gathering spatial information about affected brain areas. Elevated tau measured in cerebrospinal fluid has long been a marker of dementia, but Ances said this type of data could not pinpoint which parts of the brain are gathering abnormal proteins.

“The spinal fluid measures are very important, but they don't give us a complete spatial picture,” he said. “Our new study suggests you can tolerate a certain amount of tau clumped in the hippocampus, but once it starts spreading into other areas, especially the lateral temporal and parietal lobes, that seems to be the tipping point.”

With imaging agents for amyloid beta and now tau available, Ances said researchers have the tools necessary to assess the effectiveness of investigational therapies against the buildup of both proteins. The new agent is approved for use in the context of clinical research trials and likely will prove to be important in imaging the brain for other types of disorders that also involve excess tau buildup, including traumatic brain injury.

This study was funded by the National Institutes of Health (NIH), grant numbers P50AG05681, P01AG003991, P01AG026276, 5P30NS048056, 2UL1TR000448 and 5RO1AG04343404; the National Science Foundation (NSF), grant number DMS1300280; the Charles F. and Joanne Knight Alzheimer’s Research Initiative; the Hope Center for Neurological Disorders; the Fred Simmons and Olga Mohan Fund; and the Paula and Rodger Riney Fund.

Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly) provided florbetapir doses and partial financial support for the florbetapir scanning sessions. Avid Radiopharmaceuticals also provided the precursor for T807 and radiopharmaceutical AQ4 chemistry and technology for the Washington University Investigational New Drug, under which this study was performed.

For more information: www.stm.sciencemag.org

Related Content

Novel Technique May Significantly Reduce Breast Biopsies
News | Breast Biopsy Systems | January 17, 2019
A novel technique that uses mammography to determine the biological tissue composition of a tumor could help reduce...
Digital Mammography Increases Breast Cancer Detection
News | Mammography | January 16, 2019
The shift from film to digital mammography increased the detection of breast cancer by 14 percent overall in the United...
MIM Software Inc. Receives FDA 510(k) Clearance for Molecular Radiotherapy Dosimetry
Technology | Nuclear Imaging | January 16, 2019
MIM Software Inc. received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for molecular radiotherapy...
Artificial Intelligence Used in Clinical Practice to Measure Breast Density
News | Artificial Intelligence | January 15, 2019
An artificial intelligence (AI) algorithm measures breast density at the level of an experienced mammographer,...
Machine Learning Uncovers New Insights Into Human Brain Through fMRI
News | Neuro Imaging | January 11, 2019
An interdisciplinary research team led by scientists from the National University of Singapore (NUS) has successfully...
Mobile App Data Collection Shows Promise for Population Health Surveys
News | Population Health | January 10, 2019
Mobile app data collection can bring access to more potential clinical study participants, reduce clinical study...
Hypertension With Progressive Cerebral Small Vessel Disease Increases Cognitive Impairment Risk
News | Magnetic Resonance Imaging (MRI) | January 08, 2019
Patients with high blood pressure and progression of periventricular white matter hyperintensities showed signs of...
Artificial Intelligence Pinpoints Nine Different Abnormalities in Head Scans

A brain scan (left) showing an intraparenchymal hemorrhage in left frontal region and a scan (right) of a subarachnoid hemorrhage in the left parietal region. Both conditions were accurately detected by the Qure.ai tool. Image courtesy of Nature Medicine.

News | Artificial Intelligence | January 07, 2019
The rise in the use of computed tomography (CT) scans in U.S. emergency rooms has been a well-documented trend1 in...
Electronic Brachytherapy Effective in Long-Term Study of 1,000 Early-Stage Breast Cancers
News | Brachytherapy Systems, Women's Healthcare | January 07, 2019
Breast cancer recurrence rates of patients treated with intraoperative radiation therapy (IORT) using the Xoft Axxent...
Brachytherapy Alone Superior Treatment for Intermediate-Risk Prostate Cancer
News | Brachytherapy Systems | January 04, 2019
Patient-reported outcomes (PROs) indicated a significantly different clinician and patient-reported late toxicity...