URMC Research Provides New Insights into Relationship Between Tau Protein and Cognitive Decline

A study by University of Rochester Medical Center researchers provides new insights into the relationship between Alzheimer’s disease pathology and cognitive decline.

In a paper titled “Longitudinal stability of medial temporal lobe connectivity is associated with tau-related memory decline” published in the eLife journal, URMC researchers explore the links between the measure of phosphorylated tau (Ptau) in cerebrospinal fluid and changes in brain structural connectivity over time.

“For Ptau to become a potentially meaningful therapeutic target for preventing or slowing Alzheimer’s or other forms of dementia, we needed to better understand how tau impacts structural brain networks associated with memory decline in aging,” said Quanjing Chen, PhD, a postdoctoral associate at the University of Rochester School of Nursing and the Department of Psychiatry, who was the study’s lead author.

Alzheimer’s is a disease characterized by the presence of both amyloid-beta and tau proteins that lead to neurodegeneration. Recent research suggests that the prevalence of Ptau was a better predictor of long-term cognitive deficits, but little is known about the neurocognitive mechanisms linking Ptau with memory-related declines.

In healthy neurons, tau normally binds to and stabilizes microtubules. In Alzheimer's disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons, according to the National Institute on Aging.

Extracting data from a sample of older adults who are cognitively normal or have mild cognitive impairment, researchers found that the presence of cerebrospinal fluid Ptau at baseline was related to a loss of structural stability in medial temporal lobe connectivity in a way that matched disease progression. This loss of structural stability moderated the effect of Ptau on the rate of memory change, suggesting that structural stability in the medial temporal lobe may be an important link between the accumulation of Ptau and memory decline.

Additional authors on the study include UR researchers Adam Turnbull, PhD, of the School of Nursing and the Department of Imaging Sciences; Timothy Baran, PhD, of the Department of Imaging Sciences and Department of Biomedical Engineering; and Feng Vankee Lin, PhD, RN, of the School of Nursing, Department of Psychiatry, Department of Neuroscience, Department of Neurology, and Department of Brain and Cognitive Sciences.