(Press-News.org) JACKSONVILLE, Fla. -- By examining more than 3,600 postmortem brains, researchers at Mayo Clinic's campuses in Jacksonville, Florida, and Rochester, Minnesota, have found that the progression of dysfunctional tau protein drives the cognitive decline and memory loss seen in Alzheimer's disease. Amyloid, the other toxic protein that characterizes Alzheimer's, builds up as dementia progresses, but is not the primary culprit, they say.
The findings, published in Brain, offer new and valuable information in the long and ongoing debate about the relative contribution of amyloid and tau to the development and progression of cognitive dysfunction in Alzheimer's, says the study's lead author, Melissa Murray, Ph.D., a neuroscientist at Mayo Clinic in Jacksonville.
MULTIMEDIA ALERT: Video and audio are available for download on the Mayo Clinic News Network.
The findings also suggest that halting toxic tau should be a new focus for Alzheimer's treatment, the researchers say.
"The majority of the Alzheimer's research field has really focused on amyloid over the last 25 years," Dr. Murray says. "Initially, patients who were discovered to have mutations or changes in the amyloid gene were found to have severe Alzheimer's pathology -- particularly in increased levels of amyloid. Brain scans performed over the last decade revealed that amyloid accumulated as people progressed, so most Alzheimer's models were based on amyloid toxicity. In this way, the Alzheimer's field became myopic."
But researchers at Mayo Clinic were able to simultaneously look at the evolution of amyloid and tau using neuropathologic measures. "Imagine looking at the rings of a tree -- you can identify patterns, like the changing seasons and the aging of the tree, when viewing the tree's cross-section," Dr. Murray says. "Studying brains at different stages of Alzheimer's gives us a perspective of the cognitive impact of a wide range of both amyloid and tau severity, and we were very fortunate to have the resource of the Mayo brain bank, in which thousands of people donated their postmortem brains, that have allowed us to understand the changes in tau and amyloid that occur over time."
"Tau can be compared to railroad ties that stabilize a train track that brain cells use to transport food, messages and other vital cargo throughout neurons," Dr. Murray says. "In Alzheimer's, changes in the tau protein cause the tracks to become unstable in neurons of the hippocampus, the center of memory. The abnormal tau builds up in neurons, which eventually leads to the death of these neurons. Evidence suggests that abnormal tau then spreads from cell to cell, disseminating pathological tau in the brain's cortex. The cortex is the outer part of the brain that is involved in higher levels of thinking, planning, behavior and attention -- mirroring later behavioral changes in Alzheimer's patients."
"Amyloid, on the other hand, starts accumulating in the outer parts of the cortex and then spreads down to the hippocampus and eventually to other areas," she says. "Our study shows that the accumulation of amyloid has a strong relationship with a decline in cognition. When you account for the severity of tau pathology, however, the relationship between amyloid and cognition disappears -- which indicates tau is the driver of Alzheimer's," Dr. Murray says.
Amyloid brain scanning has been used for only about a decade, and "so there are still many unanswered questions about what it is measuring," she adds. "Investigating what brain pathology underlies the amyloid brain scanning threshold indicative of Alzheimer's can only be addressed in patients who underwent scanning and donated their brain for research."
The study was conducted in two parts. Researchers at Mayo Clinic in Florida examined 3,618 brains in its postmortem brain bank, of which 1,375 brains were Alzheimer's confirmed. These patients died at different ages and different stages of dementia, providing a valuable timeline into disease progression.
The researchers used recommended scoring systems to examine the evolution of amyloid and tau in dissected brain tissue. They found that the severity of tau, but not amyloid, predicted age onset of cognitive decline, disease duration and mental deterioration.
The second part of the study was conducted with their collaborators at Mayo Clinic in Rochester. Together the team examined amyloid brain scans taken of patients prior to death and compared the scans to measures of tau and amyloid brain pathology.
The investigators found that the signal from amyloid brain scans corresponded with amyloid pathology specific to the brain and not amyloid found in vessels, and did not correspond to tau pathology. The brains of some participants had amyloid visible at pathology that did not reach the threshold for what would be found in Alzheimer's brain scans. This is important, as amyloid can be found in brains of older individuals who have not experienced cognitive decline, researchers say.
"Our findings highlight the need to focus on tau for therapeutics, but it also still indicates that the current method of amyloid brain scanning offers valid insights into tracking Alzheimer's," Dr. Murray says. "Although tau wins the 'bad guy' award from our study's findings, it is also true that amyloid brain scanning can be used to ensure patients enrolling for clinical trials meet an amyloid threshold consistent with Alzheimer's -- in lieu of a marker for tau."
INFORMATION:
Co-authors of the study are, from Mayo Clinic in Jacksonville: Neill Graff-Radford, M.D., Amanda Liesinger, Ashley Cannon, Ph.D., Bhupendra Rawal, M.S., Owen Ross, Ph.D., and Dennis Dickson, M.D.; from Mayo Clinic in Rochester: Val Lowe, M.D., Scott Przybelski, Joseph Parisi, M.D., Ronald Petersen, M.D., Ph.D., Kejal Kantarci, M.D., David Knopman, M.D., and Clifford Jack, Jr., M.D.; and Ranjan Duara, M.D., from Mount Sinai Medical Center.
The study was funded by the National Institutes of Health (R01-AG040042, R01-AG011378, R01-AG041851, P50- AG016574, U01-AG006786, P50-NS072187), The Mangurian Foundation, the Robert H. and Clarice Smith and Abigail vanBuren Alzheimer's Disease Research Program, the Elsie and Marvin Dekelboum Family Foundation, the Donors Cure Foundation New Vision Award, and The Alexander Family.
About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to medical research and education, and providing expert, whole-person care to everyone who needs healing. For more information, visit mayoclinic.com or newsnetwork.mayoclinic.org.
Chicago, March 24, 2015 - The Alzheimer's Association's 2015 Alzheimer's Disease Facts and Figures report, released today, found that only 45 percent of people with Alzheimer's disease or their caregivers say they were told the diagnosis by their doctor. In contrast, more than 90 percent of people with the four most common cancers (breast, colorectal, lung and prostate cancer) say they were told the diagnosis.
"These disturbingly low disclosure rates in Alzheimer's disease are reminiscent of rates seen for cancer in the 1950s and 60s, when even mention of the word cancer ...
A previously undiscovered species of crocodile-like amphibian that lived during the rise of dinosaurs was among Earth's top predators more than 200 million years ago, a study shows.
Palaeontologists identified the prehistoric species - which looked like giant salamanders - after excavating bones buried on the site of an ancient lake in southern Portugal.
The species was part of a wider group of primitive amphibians that were widespread at low latitudes 220-230 million years ago, the team says.
The creatures grew up to 2m in length and lived in lakes and rivers during ...
Suicidal patients who are under observation may be put at risk by relying on inexperienced staff and agency nurses, according to a new report issued today.
Commissioned by the Healthcare Quality Improvement Partnership as part of the Clinical Outcome Review Programmes, researchers from The University of Manchester's National Confidential Inquiry into Suicide and Homicide by People with Mental Illness, found that 18 in-patients a year died by suicide while under observation. This usually meant checks every 10-15 minutes but in 9% the patient was supposed to be under constant ...
Effective tuberculosis control in India needs political will and commitment, backed by sufficient resources, says a senior doctor in The BMJ this week.
Unless this happens, TB will continue to be India's silent epidemic and a death sentence for poor people, warns consultant physician and public health specialist, Zarir Udwadia.
Twenty years ago it was widely believed that India was successfully on its way to controlling its alarming tuberculosis (TB) epidemic. Yet, each year, India has 2.2 million new cases, more than 300,000 deaths, and economic losses of $23bn (£14.9bn; ...
Conscientious children are less likely to smoke in later life and the personality trait could help explain health inequalities, indicates a study published in the Journal of Epidemiology & Community Health.
It is well known that people belonging to lower socio-economic groups have lower life expectancy and more health problems than those who are in higher groups, and certain health behaviours, such as smoking, follow a similar pattern, suggesting they could be partly responsible for health inequalities.
Recently, certain personality traits have been found to be associated ...
At least 30 dogs in England have been killed in less than 18 months by an unknown disease which causes skin lesions and kidney failure, reveals research published in Veterinary Record.
The disease is believed to be Alabama rot (cutaneous and renal glomerular vasculopathy), a condition which has been seen in the USA in greyhounds for almost 30 years.
While there have been occasional reports of the disease in individual dogs outside of the USA, this is the first report of a series of cases occurring in England. None of the 30 dogs in this English series of cases were greyhounds ...
On May 19, 2014, the 67th World Health Assembly (WHA) adopted WHO's "Global strategy and targets for tuberculosis prevention, care and control after 2015". This post-2015 global tuberculosis strategy, labelled the End TB Strategy, was shaped during the past 2 years. A wide range of stakeholders--from ministries of health and national tuberculosis programmes to technical and scientific institutions, financial and development partners, civil society and health activists, non-governmental organisations, and the private sector--contributed to its development. The strategy has ...
Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. This study, led by Dr Anne Detjen, from the International Union Against Tuberculosis and Lung Disease, aimed to establish summary estimates for sensitivity and specificity of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children. The researchers found that compared with microscopy, Xpert offers better sensitivity for the diagnosis of pulmonary ...
1. Task Force finds insufficient evidence to recommend routine screening for thyroid dysfunction
The U.S. Preventive Services Task Force (USPSTF) concludes that the current evidence is insufficient to recommend for or against screening for thyroid dysfunction in nonpregnant, asymptomatic adults. The recommendations are published in Annals of Internal Medicine.
Thyroid gland disorders are among the most common endocrine conditions evaluated and treated by clinicians and may be asymptomatic. If left untreated, thyroid dysfunction could lead to fractures, cancer, or cardiovascular ...
Archaeologists working in Guatemala have unearthed new information about the Maya civilization's transition from a mobile, hunter-gatherer lifestyle to a sedentary way of life.
Led by University of Arizona archaeologists Takeshi Inomata and Daniela Triadan, the team's excavations of the ancient Maya lowlands site of Ceibal suggest that as the society transitioned from a heavy reliance on foraging to farming, mobile communities and settled groups co-existed and may have come together to collaborate on construction projects and participate in public ceremonies.
The findings, ...
