Subclinical Brain Levels of Amyloid Predict Tau Deposition in Aging

By Will Boggs MD

NEW YORK—Subclinical accumulation of amyloid in the brain predicts subsequent tau deposition in brain areas associated with Alzheimer disease, according to a PET study.

"One of the most interesting things we found was that rate of change in amyloid, but even baseline amyloid levels, in individuals who are considered to be 'amyloid negative' could significantly predict whether or not someone would develop tau later on," said Dr. Stephanie L. Leal from the University of California, Berkeley.

"This suggests that we need to view these amyloid measures on a continuum, rather than assuming individuals who are considered amyloid negative are aging healthily," she told Reuters Health by email.

Amyloid deposits in the brain, in the form of beta-amyloid plaques, precede the emergence of Alzheimer disease (AD) symptoms by decades, and widespread tau deposition is associated with cognitive decline and progression to AD.

Dr. Leal and colleagues used PET imaging to investigate the earliest stages of AD pathology and to determine whether it's possible to predict subsequent tau deposition and memory decline in cognitively normal older adults.

They found an inverted-U relationship between baseline amyloid-beta and amyloid-beta slope in these older adults, which suggested a slowing of amyloid-beta accumulation with age in cognitively normal adults similar to that seen in individuals with mild cognitive impairment (MCI) or AD.

Baseline levels of amyloid and beta-amyloid accumulation strongly predicted subsequent tau deposition over a period of about five years in brain regions associated with AD, the researchers report in The Journal of Neuroscience, online April 23.

Even subthreshold levels of amyloid-beta predicted tau deposition.

Memory decline developed only in association with higher levels of amyloid-beta, suggesting that memory impairment develops after AD pathology has begun to spread.

"Together, these results indicate that AD is beginning in those who are nominally 'amyloid negative,' and by the time high levels of brain amyloid-beta eventuate, the rate of accumulation is already slowing," the researchers note.

"Clinical trials in individuals with preclinical Alzheimer's disease, those who are cognitively normal but have amyloid in their brains, has been a huge step in the right direction," Dr. Leal said. "However, our findings indicate that some of these individuals may already be slowing down their rate of amyloid accumulation, even though they remain cognitively intact. Inclusion of those with very low amyloid levels may enhance our ability to slow disease progression before too much damage is done."

"Early detection of Alzheimer's disease is quite difficult, especially since these subtle pathological changes are likely occurring decades before any clinical symptoms appear," she said. "Following individuals longitudinally is very important in detecting these subtle changes in pathology or cognition, and hopefully these tools will become available as biomarkers to determine the optimal time to intervene with treatments and interventions to slow disease progression once these treatments become available."

Dr. Niklas Mattsson from Lund University in Sweden, who has studied tau and its relationship to AD but was not involved in the new research, told Reuters Health by email, "The finding that amyloid and tau accumulation are coupled already early in the disease course is an interesting finding with potentially important implications both for our understanding of the disease mechanisms and for development of new therapies."

"The findings support very early interventions against the pathological proteins that accumulate in Alzheimer's disease," he said. "Hypothetically, the window of opportunity may be quite short before amyloid accumulation results in downstream effects on tau."

"As clinicians and researchers in this field, we can continue to work with clinical trials of candidate treatments against amyloid and tau, even in people with very little or no symptoms, to develop prevention therapies against Alzheimer's disease," Dr. Mattsson said.

SOURCE: https://bit.ly/2r3q4xT

J Neurosci 2018.

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