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Abstract Details

White Matter Hyperintensities and TDP-43 Pathology in Alzheimer's Disease
Aging, Dementia, and Behavioral Neurology
P4 - Poster Session 4 (5:00 PM-6:00 PM)
3-007
To determine whether white matter hyperintensity (WMH) burden on MRI would correlate with transactive response DNA-binding protein 43 (TDP-43) pathology in Alzheimer’s disease (AD-TDP), and whether associations would vary in younger versus older participants.
There are two main types of AD-TDP lesions: type-α, which closely resembles lesions in frontotemporal lobar degeneration with TDP-43 (FTLD-TDP); and type-β, which shows co-deposition with tau in the setting of higher AD neuropathologic changes. Greater WMH are seen with FTLD-TDP but its associations with AD-TDP remain unclear.

One-hundred fifty-seven participants from Mayo Clinic Study of Aging, Alzheimer’s Disease Research Center, and Neurodegenerative Research Group with autopsy-confirmed AD, known TDP-43 status/typing, and antemortem FLAIR MRI were included. A semi-automated WMH segmentation and quantification process was used to obtain total and regional WMH volumes from periventricular and subcortical regions of the frontal, temporal, parietal, and occipital lobes, and basal ganglia. Multiple linear regression models adjusting for age at MRI were used to assess TDP-43 pathology associations (status and typing) across all, younger (<80y), and older (≥80y) participants.
Fifty percent (78/157) of participants were TDP-43-positives (60% type-α, 40% type-β). Median age at MRI was 83y for all (72y for young, 87y for old). TDP-43-positive status was not associated with total or regional WMH burden overall because opposite effects were seen based on AD-TDP typing. AD-TDP type-α showed 13% greater total and 30-43% greater regional WMH burden in subcortical fronto-temporal regions and basal ganglia (all P<0.05) than TDP-43-negatives. Compared to type-β, type-α also showed 33% greater total WMH likely driven by greater burden in periventricular fronto-temporo-parietal regions (16-26%) and subcortical parieto-occipital (19-49%) and fronto-temporal (70%) regions (all P<0.02). These effects appear to be driven by changes in the younger cohort. 
AD-TDP types may have different WMH pathomechanisms especially in younger participants, with type-α having associations like those of FTLD-TDP.
Authors/Disclosures
Arenn Faye Carlos, MD (Nebraska Medical Center (UNMC))
PRESENTER 		The institution of Dr. Carlos has received research support from 好色先生.
Nha Trang Thu Pham (Mayo Clinic) Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic.
Ronald C. Petersen, MD, PhD, FAAN (Mayo Clinic) Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co.. Dr. Petersen has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai, Inc.. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has a non-compensated relationship as a Board of Directors with American Brain Foundation that is relevant to AAN interests or activities.
Clifford R. Jack, Jr., MD (Mayo Clinic) The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Dennis W. Dickson, MD (Mayo Clinic) Dr. Dickson has nothing to disclose.
Jennifer Whitwell, PhD (Mayo Clinic) The institution of Dr. Whitwell has received research support from NIH.
Keith A. Josephs, Jr., MD, FAAN (Mayo Clinic) Dr. Josephs has nothing to disclose.