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Workshop: Gaps and Opportunities Related to Clinical Detection of Limbic-predominant Age-related TDP-43 Encephalopathy (LATE)

Audience

Researchers interested in learning more about clinical detection of Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).

Dates

May 25, 2023 | 10 a.m. - 6 p.m. ET

Purpose and background

Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) is a recently described brain disorder that is related to the slow progression of memory loss in aging, thereby mimicking the clinical features of Alzheimer’s disease. It is very common in older adults on its own and even more common in conjunction with Alzheimer’s Disease where it is associated with even faster decline in memory and other aspects of thinking.  There are pathological (autopsy) diagnostic and staging criteria for LATE, but we do not currently have criteria for diagnosis in people during life. This workshop examined the gaps and opportunities related to the clinical detection of LATE both on its own and in conjunction with Alzheimer’s Disease and Related Dementias. Focus included the latest knowledge on the clinical manifestations of LATE and biomarkers for its detection.  In light of emerging therapeutics targeting Alzheimer’s Disease specifically, distinguishing LATE from AD during life is a gap that needs to be filled and will facilitate development of LATE directed therapies. This meeting convened neuropsychologists, neurologists, imagers, pathologists, geneticists, statisticians and NGOs.

Four subcommittees were established to meet in advance of the meeting and discuss appropriate presentations for each section of the agenda. The subcommittee members continued discussion for a second day following the workshop to summarize the workshop and address any remaining questions.

Meeting recordings

Gaps and Opportunities Related to Clinical Detection of LATE: Part 1 - YouTube

Gaps and Opportunities Related to Clinical Detection of LATE: Part 2 - YouTube

Meeting summary

Read the Clinical Detection of LATE Meeting Summary.

Agenda

Note: This agenda is in Eastern Daylight Time.

Thursday, May 25, 2023

10:00 a.m. Opening Remarks

  • Purpose of Workshop and Goals, David Wolk, M.D., University of Pennsylvania 
  • Scope of Problem: Clinical-pathologic and epidemiology perspective, Julie Schneider, M.D., M.S., Rush University Medical Center
  • Definition/Background Relating Pathology and Clinical Factors, Pete Nelson, M.D., Ph.D., University of Kentucky 
  • Q&A and Discussion

11:00 a.m. Neuropsychology and Clinical Characteristics Subcommittee

  • LATE: The Cognitive Impact and Profile, Patricia Boyle, PhD, Rush University and Lei Yu, PhD, Rush University
  • The Prevalence and Malignancy of LATE in The 90+ Study, Claudia Kawas, MD, UC Irvine
  • Discussion

12:00 p.m. Break

1:00 p.m. Biomarkers and Imaging Subcommittee 

  • Plasma and CSF Biomarkers for TDP-43, Robert Rissman, PhD, University of Southern California and Henrik Zetterberg, MD, PhD, University of Wisconsin/ University of Gothenburg
  • Magnetic Resonance Imaging Markers of LATE, Konstantinos Arfanakis, PhD, Rush University Medical Center / Illinois Institute of Technology
  • (FDG-)PET Biomarkers of LATE, Michel Grothe, PhD, Instituto de Biomedicina de Sevilla/ University of Gothenburg, Sweden

2:00 p.m. Integration of Neuropsychology and Biomarkers towards a Clinical Diagnosis of LATE

  • Retrospective Pathologic Evaluation of a LATE Clinical Syndrome Score, David Jones, MD, Mayo Clinic
  • Discussion

3:00 p.m. Break

3:15 p.m. Genetic Predictors and Risk Factors Subcommittee

  • Overview of LATE-NC Genetic Risk Factors, Pete Nelson, MD, PhD, University of Kentucky
  • GRN and TMEM106B in LATE-NC and FTLD-TDP Type A, Rosa Rademakers, PhD, University of Antwerp
  • APOE in LATE-NC and ADNC, Hyun-Sik Yang, MD, Brigham and Women's Hospital/ Harvard Medical School
  • Gaps and opportunities related to LATE-NC genetic research, Dave Fardo, PhD, University of Kentucky
  • Discussion

4:15 p.m. Clinical Trials Subcommittee

  • Conceptualizing Clinical Trials for LATE and LATE+, Greg Jicha, MD, PhD, University of Kentucky 
  • Trial Design Considerations in the Era of LATE, Rema Raman, PhD, University of Southern California 
  • Discussion

5:15 p.m. Overall Discussion

Contact information

Please contact Dr. Nina Silverberg (silverbergn@mail.nih.gov) and Dr. Aleksandra Dakic (aleksandra.dakic@nih.gov) for questions you may have about the workshop.

Additional information

nia.nih.gov

An official website of the National Institutes of Health