Pure LATE-NC: Frequency, clinical impact, and the importance of considering APOE genotype when assessing this and other subtypes of non-Alzheimer's pathologies.

Autor: Katsumata Y; Department of Biostatistics, University of Kentucky, Lexington, KY, 40536-0679, USA.; Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA., Wu X; Department of Biostatistics, University of Kentucky, Lexington, KY, 40536-0679, USA.; Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA., Aung KZ; Department of Biostatistics, University of Kentucky, Lexington, KY, 40536-0679, USA.; Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA., Fardo DW; Department of Biostatistics, University of Kentucky, Lexington, KY, 40536-0679, USA.; Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA., Woodworth DC; Department of Neurology, University of California, Irvine, CA, 92,697, USA., Sajjadi SA; Department of Neurology, University of California, Irvine, CA, 92,697, USA.; Department of Pathology, University of California, Irvine, CA, 92,697, USA., Tomé SO; Laboratory for Neuropathology, Department of Imaging and Pathology and Leuven Brain Institute, KU Leuven, Leuven, Belgium., Thal DR; Laboratory for Neuropathology, Department of Imaging and Pathology and Leuven Brain Institute, KU Leuven, Leuven, Belgium.; Department of Pathology, University Hospitals Leuven, Leuven, Belgium., Troncoso JC; Departments of Pathology and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Chang K; Departments of Pathology and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Mock C; National Alzheimer's Coordinating Center (NACC), University of Washington, Seattle, WA, USA., Nelson PT; Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA. pnels2@email.uky.edu.; Department of Pathology, Division of Neuropathology, University of Kentucky, Rm 575 Lee Todd Bldg, U. Kentucky, 789 S. Limestone Ave., Lexington, KY, 40536-0230, USA. pnels2@email.uky.edu.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Nov 15; Vol. 148 (1), pp. 66. Date of Electronic Publication: 2024 Nov 15.
DOI: 10.1007/s00401-024-02821-y
Abstrakt: Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer's disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer's Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses. For > 90% of these participants, apolipoprotein E (APOE) allele status was known; 46.5% had at least one APOE 4 allele. In most human populations, only 15-25% of people are APOE ε4 carriers. ADRCs with higher documented AD risk allele (APOE or BIN1) rates had fewer participants lacking ADNC, and correspondingly low rates of pure LATE-NC. Among APOE ε4 non-carries, 5.3% had pure LATE-NC, 37.0% had pure ADNC, and 3.6% had pure neocortical Lewy body pathology. In terms of clinical impact, participants with pure LATE-NC tended to die after having received a diagnosis of dementia: 56% died with dementia among APOE ε4 non-carrier participants, comparable to 61% with pure ADNC. LATE-NC was associated with increased Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores, i.e. worsened global cognitive impairments, in participants with no/low ADNC and no neocortical Lewy body pathology (p = 0.0023). Among pure LATE-NC cases, there was a trend for higher LATE-NC stages to be associated with worse CDR-SOB scores (p = 0.026 for linear trend of LATE-NC stages). Pure LATE-NC was not associated with clinical features of disinhibition or primary progressive aphasia. In summary, LATE-NC with no or low levels of ADNC was less frequent than pure ADNC but was not rare, particularly among individuals who lacked the APOE 4 allele, and in study cohorts with APOE 4 frequencies similar to those in most human populations.
Competing Interests: Declarations Conflict of interest DRT & SOT received consultant honorary from Muna Therapeutics (Belgium). DRT collaborated with Novartis Pharma AG (Switzerland), and GE-Healthcare (UK). DRT and PTN are members of Acta Neuropathologica editorial board. They were not involved in the assessment or decision-making process for this manuscript. The other authors declare that they have no competing interests. Ethical approval and consent to participate For all NACC data, only anonymized summary information was used. Institutional review board approval and informed consent were obtained from all participants at each of individual AD Research Center (ADRC). Under those auspices, informed consent was obtained from all individual participants included in the study. See https://naccdata.org/requesting-data/nacc-data Consent for publication Not applicable.
(© 2024. The Author(s).)
Databáze: MEDLINE
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