Abstract
Transactive response DNA-binding protein 43kDa (TDP-43) is aberrantly aggregated and phosphorylated in frontotemporal lobar degeneration of the TDP-43 type (FTLD-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). We examined data from the National Alzheimer's Coordinating Center to compare clinical features of autopsy-confirmed LATE-NC and FTLD-TDP. A total of 265 LATE-NC and 92 FTLD-TDP participants were included. Cognitive and behavioral symptoms were compared, stratified by level of impairment based on global clinical dementia rating (CDR) score. LATE-NC participants were older at death, more likely to carry APOE e4, more likely to have Alzheimer disease neuropathology, and had lower (i.e. less severe) final CDR global scores than those with FTLD-TDP. Participants with FTLD-TDP were more likely to present with primary progressive aphasia, or behavior problems such as apathy, disinhibition, and personality changes. Among participants with final CDR score of 2-3, those with LATE-NC were more likely to have visuospatial impairment, delusions, and/or visual hallucinations. These differences were robust after sensitivity analyses excluding older (≥80 years at death), LATE-NC stage 3, or severe Alzheimer cases. Overall, FTLD-TDP was more globally severe, and affected younger participants, whereas psychoses were more common in LATE-NC.
| Original language | English |
|---|---|
| Pages (from-to) | 1024-1032 |
| Number of pages | 9 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 80 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2021 |
Bibliographical note
Publisher Copyright:© 2021 American Association of Neuropathologists, Inc. All rights reserved.
Funding
The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Say-kin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paul-son, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). Dr. Nelson is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. Dr. Katsumata is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK-ADC P30AG028383 from the National Institute on Aging. We are grateful to the research volunteers, their families and caregivers, and our colleagues at the NIA-funded Alzheimer's Disease Research Centers.
| Funders | Funder number |
|---|---|
| UK-ADC | P30AG028383 |
| National Institutes of Health (NIH) | P30 AG013846, P30 AG028383, P30 AG008017, P30 AG053760, R01AG057187, P30 AG010133, P50 AG005146, P50 AG033514, P50 AG005142, P50 AG005681, R56AG057191, P50 AG047366, P50 AG047266, R21AG061551, P30 AG019610, RF1 NS118584, P50 AG023501, P30 AG008051, P30 AG010129, P30 AG013854, P50 AG005138, P50 AG008702, P30 AG010124, P30 AG012300, P50 AG005134, P50 AG005136, P50 AG025688, P50 AG047270, R01AG054060, U01 AG016976, P30 AG035982, P30 AG010161, P50 AG005131, P50 AG005133, P30 AG049638, P50 AG016574, P50 AG016573, R01 AG061111 |
| National Institute on Aging | U24AG072122 |
Keywords
- FTD
- Frontotemporal
- Neuropsychiatric
- Plaques
- Tangles
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience