Abstract
Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.
| Original language | English |
|---|---|
| Pages (from-to) | 975-987 |
| Number of pages | 13 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 81 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2022 |
Bibliographical note
Publisher Copyright:© 2022 The Author(s).
Funding
PTN is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. YK is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK-ADC P30AG028383 from the National Institute on Aging. The NACC database is funded by NIA/NIH grant U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P50 AG005131 (PI James Brewer, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005138 (PI Mary Sano, PhD), P50 AG005142 (PI Helena Chui, MD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005681 (PI John Morris, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG008051 (PI Thomas Wisniewski, MD), P50 AG008702 (PI Scott Small, MD), P30 AG010124 (PI John Trojanowski, MD, PhD), P30 AG010129 (PI Charles DeCarli, MD), P30 AG010133 (PI Andrew Saykin, PsyD), P30 AG010161 (PI David Bennett, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG013854 (PI Robert Vassar, PhD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG019610 (PI Eric Reiman, MD), P50 AG023501 (PI Bruce Miller, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG028383 (PI Linda Van Eldik, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P30 AG035982 (PI Russell Swerdlow, MD), P50 AG047266 (PI Todd Golde, MD, PhD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG049638 (PI Suzanne Craft, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Marwan Sabbagh, MD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), and P30 AG072959 (PI James Leverenz, MD).
| Funders | Funder number |
|---|---|
| UK-ADC | |
| National Institutes of Health (NIH) | RF1 NS118584, R01 AG061111 |
| National Institutes of Health (NIH) | |
| National Institute on Aging | P30 AG013846, P30 AG008017, P30 AG053760, R01AG057187, P30 AG010133, P50 AG005146, P50 AG033514, P50 AG005142, P50 AG005681, R56AG057191, P50 AG047366, P50 AG047266, R21AG061551, P20 AG068053, P20 AG068077, P30 AG019610, P50 AG023501, P30 AG008051, P30 AG010129, P30 AG013854, P30 AG072958, P30 AG072959, P50 AG005138, P50 AG008702, P30 AG010124, P30 AG012300, P50 AG005134, P50 AG005136, P50 AG025688, P50 AG047270, R01AG054060, P30 AG035982, P30 AG010161, P50 AG005131, P50 AG005133, P30 AG049638, P30AG028383, P50 AG016574, P20 AG068082, P30AG066546, U24 AG072122, P20 AG068024, P50 AG016573 |
| National Institute on Aging |
Keywords
- Alzheimer disease
- Depression
- Lewy body
- Limbic predominant age-related TDP-43 encephalopathy
- Neuropsychiatric
- TDP-43
ASJC Scopus subject areas
- General Medicine