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Comprehensive assessment of TDP-43 neuropathology data in the National Alzheimer’s Coordinating Center database

  • Davis C. Woodworth
  • , Katelynn M. Nguyen
  • , Lorena Sordo
  • , Kiana A. Scambray
  • , Elizabeth Head
  • , Claudia H. Kawas
  • , María M. Corrada
  • , Peter T. Nelson
  • , S. Ahmad Sajjadi

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer’s Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%). Regional TDP-43 pathologic assessment was available for 77% of participants, with hippocampus the most common region. Availability for the TDP-43-related measures increased over time, and was higher in centers with high proportions of participants with clinical FTLD. Part II: In 2142 participants with all TDP-43-related assessments available, 27% of participants had LATE-NC, whereas ALS-TDP or FTLD-TDP (ALS/FTLD-TDP) was present in 9% of participants, and 2% of participants had TDP-43 related to other pathologies (“Other TDP-43”). HS-A was present in 14% of participants, of whom 55% had LATE-NC, 20% ASL/FTLD-TDP, 3% Other TDP-43, and 23% no TDP-43. LATE-NC, ALS/FTLD-TDP, and Other TDP-43, were each associated with higher odds of dementia, HS-A, and hippocampal atrophy, compared to those without TDP-43 pathology. LATE-NC was associated with higher odds for Alzheimer’s disease (AD) clinical diagnosis, AD neuropathologic change (ADNC), Lewy bodies, arteriolosclerosis, and cortical atrophy. ALS/FTLD-TDP was associated with higher odds of clinical diagnoses of primary progressive aphasia and behavioral-variant frontotemporal dementia, and cortical/frontotemporal lobar atrophy. When using NACC data for TDP-43-related analyses, researchers should carefully consider the incomplete availability of the different regional TDP-43 assessments, the high frequency of participants with ALS/FTLD-TDP, and the presence of other forms of TDP-43 pathology.

Original languageEnglish
Article number103
JournalActa Neuropathologica
Volume147
Issue number1
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Funding

The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD).

FundersFunder number
National Institute on Aging
National Institutes of Health (NIH)P30 AG062677, P30 AG066514, P30 AG066515, P30 AG066518, P30 AG066519, P30 AG062715, P20 AG068053, P30 AG066462, P30 AG072931, P30 AG072975, P20 AG068077, P30 AG072976, P30 AG072977, P30 AG066444, P30 AG072972, P30 AG066468, P30 AG072973, P30 AG072978, P30 AG072979, P30 AG072958, P30 AG072959, P30 AG062421, P30 AG079280, P30 AG062422, P30 AG066546, P30 AG066506, P30 AG066507, P30 AG066508, P30 AG062429, P30 AG066509, P30 AG066530, P20 AG068082, P30 AG066511, P30 AG066512, U24 AG072122, P20 AG068024, P30 AG072946, P30 AG072947
National Institutes of Health (NIH)

    Keywords

    • Alzheimer’s disease
    • Amyotrophic lateral sclerosis
    • Dementia
    • Frontotemporal lobar degeneration
    • Hippocampal sclerosis of aging
    • Limbic predominant age-related TDP-43 encephalopathy neuropathologic change
    • National Alzheimer’s coordinating center
    • TDP-43

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Clinical Neurology
    • Cellular and Molecular Neuroscience

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