“LATE”- a New Diagnosis That May Improve Dementia Care For Older People

Diagnosing Dementia in older adults is difficult because many individuals have multiple medical conditions with symptoms that include some degree of cognitive impairment. Recently, research has focused on a form of Dementia that generally develops slowly in adults in their 80s and 90s. Called “LATE”; it is believed to affect about ten percent of people over 65, and about 20 to 50 percent of those aged 85 and older. (1)

LATE can be confused with Alzheimer’s disease (AD) because it also typically involves memory loss, but symptoms of LATE are generally limited to impaired memory and difficulty finding words or naming objects. AD, in contrast, typically progresses, affecting the ability to plan, organize, and perform tasks, as well as causing mood and behavioral changes.

What is LATE?

The longer an older person’s symptoms are limited to forgetting, without the development of significant other cognitive features, the likelier the correct diagnosis is LATE. (2) LATE is an abbreviation for “Limbic-predominant age-related TDP-43 encephalopathy”, and TDP-43 is a protein that can become toxic. This disease involves abnormal clumps of the protein that accumulate in the brain and disrupt the cell’s vital functions, resulting in the death of neurons (the brain cells that control everything we think, feel, and do).

Neuron death also occurs in AD as a result of the abnormal accumulation in the brain of two other toxic proteins, amyloid and tau. With the development of anti-amyloid therapies for AD, misdiagnosing LATE as AD could subject patients to unnecessary therapeutic risks and may cause them to miss out on effective therapy.

How Is LATE Diagnosed?

There is currently no validated test or biomarker to detect abnormal accumulations of TDP-43 in a living person. LATE must be considered as a possible diagnosis of Dementia in an older adult if imaging of the brain reveals significant atrophy of the hippocampus, which is a consistent symptom of LATE. (5) Also suggestive of LATE would be Dementia but the absence or scarcity of the AD biomarker amyloid, and especially the absence of the AD biomarker tau.

The population of people over age 85 is predicted to continue to increase substantially in the near future, and LATE is likely to become a public health burden unless effective preventative and therapeutic strategies are developed. Encouragingly, there are signs of progress. A clinical trial in the United Kingdom is evaluating a treatment designed to target the underlying disease process, offering hope for future therapies. At the same time, the development of blood-based tests and PET imaging markers for TDP-43 has become a major scientific priority, and these new diagnostic tools are on the horizon. (4) These advances offer reasons for cautious optimism that accessible diagnosis and treatment of LATE may soon be within reach.

Author: Carol A. Butler, Ph.D. cabutler@seetheotherside.org

December, 2025

References

1) Hoffman, M. 2019. Diagnostic guidelines developed for LATE, new Alzheimer-like brain disorder. www.neurologylive.com. Accessed December 21, 2025.

2) Nag, S. et al. 2017. TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD. Neurology. Feb 14:88(7),653-660. https://doi.org/10.1212/WNL.0000000000003610

3) Nelson, P. et al. 2019. Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain. 142,1503-1527.

4) Vokali, E. et al. 2025. Discovery and preclinical development of (18F)ACI-19626, a first-in-class TDP-43 tracer. Nature Communications. 16, 9358. https://doi.org/10.1038/s41467-025-64540-6

5) Wolk, D. et al. 2025. Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy. Alzheimer's Dementia, Jan:21(1).e14202. https://doi.org/10.1002/alz.1420

---

Disclaimer: Dementia Society of America (DSA) provides educational content only and does not offer medical advice. Always consult a qualified healthcare professional before making changes to your medical care. DSA content is created by both human and computer-generated means and is reviewed for accuracy; however, errors may occur. Views expressed by third-party contributors do not necessarily reflect those of DSA. Unless expressly stated, DSA does not endorse or guarantee any third-party products, services, organizations, or external content. All DSA content is copyrighted and/or trademarked and may not be used without written permission.