Abstract Details

Title Braak Neurofibrillary Tangle Staging Prediction Using In Vivo MRI Metrics

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-007

Objective

We aimed to examine the validity of cross-sectional regional metrics to predict postmortem neurofibrillary degeneration staging from in vivo brain magnetic resonance imaging (MRI).

Background

A definitive diagnosis of Alzheimer’s disease (AD) can only be established following postmortem examination. A current accepted assessment method is the “ABC staging scheme”, which requires the neuropathological gradation of (a) diffuse amyloid plaques, (b) neurofibrillary tangles (NFT), and (c) neuritic plaques. Among all pathological features of AD, the strongest correlate of brain atrophy on MRI appears to be NFT pathology. There is an evident need for the development of new biomarkers that could be used to detect the presence of AD pathology in preclinical stages of the disease.

Design/Methods We selected participants from three databases (ADNI, NACC and Rush Memory and Aging Project) providing both antemortem MRI scans and postmortem neuropathological data. After initial quality control, 186 participants were included. Bilateral surfaces, thicknesses and volumes from cortical and subcortical brain structures were extracted using FreeSurfer 5.3. Spearman’s rank correlation tests and multivariable support vector machine classification were performed to create a predictive model of the severity and distribution of AD-associated neurofibrillary degeneration.

Results We demonstrated that 59 of our 232 MRI variables were significantly associated with Braak stages (p<.005), which mostly included temporal lobe structures. We obtained a global accuracy of 62.4% to predict Braak transentorhinal (I-II), limbic (III-IV), and isocortical (V-VI) stages from cross-sectional brain metrics extracted from last MRI before death. Sex, age at scan, time interval between MRI and death, and APOE4 status were also considered in our model.

Conclusions Regional atrophy detected by in vivo brain imaging reflects underlying severity and distribution of AD-associated neurofibrillary degeneration. In vivo MRI metrics may therefore be considered as a potential biomarker for the prediction of AD neuropathological staging in the living brain.

Authors/Disclosures
Caroline Dallaire-Théroux, MD, PhD PRESENTER	Dr. Dallaire-Théroux has received research support from Canadian Institutes of Health Research (CIHR).
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Simon Duchesne, PhD (CRULRG)	Dr. Duchesne has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Qynapse SAS. Dr. Duchesne has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Nature Group. Dr. Duchesne has received stock or an ownership interest from Qynapse SAS. Dr. Duchesne has received intellectual property interests from a discovery or technology relating to health care.

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