HAI Book 2025 - Flipbook - Page 269
Moloney, Christina
Tau-PET, structural MRI, and cognitive measures are differentially
correlated with tangle and neuritic pathology across the neurofibrillary
tangle lifespan
Christina M. Moloney1, Matthew H. Rutledge2, Zhongwei Peng2, Ashley C. Wood1, Darren M.
Rothberg1, Jessica F. Tranovich1, Scott A. Przybelski3, Ekaterina I. Hofrenning3, Mary M.
Machulda4, Ronald C. Petersen5, Clifford R. Jack Jr6, Aivi T. Nguyen7, R. Ross Reichard7,
Prashanthi Vemuri6, Dennis W. Dickson1,8, Nicholas M. Kanaan9, Rickey E. Carter2, Val J.
Lowe6, Melissa E. Murray1,8
1
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, US
Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, US
3
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, US
4
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, US
5
Department of Neurology, Mayo Clinic, Rochester, MN, US
6
Department of Radiology, Mayo Clinic, Rochester, MN, US
7
Department of Laboratory Medicine and Pathology, Rochester, MN, US
8
Department of Laboratory Medicine and Pathology, Jacksonville, FL, US
9
Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI,
US
2
Objectives: The neurofibrillary tangle lifespan is defined by three maturity levels: pretangles, mature tangles, and
ghost tangles. A gap in knowledge exists regarding the type of tau pathology and tangle maturity levels the
antemortem measures reflect. We aimed to compare tangle and neuritic burden of 15 tau antibodies that range
through the tangle lifespan with 18F-Flortaucipir (tau-PET) standard uptake value ratio (SUVr), structural MRI
(sMRI), and cognitive measures.
Methods: Posterior hippocampus serial sections of cases (n=27) with antemortem measures acquired within 3
years of death were stained with 15 tau antibodies, which recognize either pan-tau, or specific phosphorylated,
conformational, and truncation epitopes. We used GENIE pattern recognition to separately quantify tangle and
neuritic pathology burden. Neuroimaging measures included tau-PET SUVr) and sMRI cortical thickness or
hippocampal volume. Memory, global cognition, and dementia severity were assessed with the Auditory-Verbal
Learning Test (AVLT), Mini-Mental State Exam (MMSE), and Clinical Dementia Rating (CDR), respectively.
Results: Tau-PET correlated moderately to strongly with tangle and neuritic pathology for markers across the
tangle lifespan, with the strongest correlations for middling tangle maturity markers (Figure). sMRI correlated
moderately with tangle burden of middling/advanced tangle maturity markers, and some early tangle maturity
markers. sMRI correlated moderately with neuritic burden for fewer antibodies. AVLT strongly correlated with
tangle and neuritic pathology throughout the tangle lifespan. MMSE weakly correlated with antibodies through the
tangle lifespan, with most significant correlations in the cortices and with neuritic pathology. CDR significantly
correlated with tangle burden of advanced tangle maturity marker MN423 in the fusiform.
Conclusions: These suggest that antemortem measures differentially correlate with specific types of tau
pathology along the tangle lifespan. These findings aid in understanding what these antemortem measures
reflect, which will have implications when interpreting future treatments.
HAI2025 - 269
