New Diagnostic Guidelines for LATE: A Breakthrough in Dementia Research
In a groundbreaking development, researchers have established clear guidelines to diagnose Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), a lesser-known but prevalent form of dementia.This advancement, led by Dr. David Wolk, co-director of the Penn Memory center, aims to improve patient care and guide treatment decisions, particularly as new therapies for Alzheimer’s disease (AD) become available.
“Clear guidelines to diagnose different diseases not only help inform patients and their families of their prognosis but also help to guide decisions about wich treatments to pursue,” said Dr. Wolk. “As therapies that clear the amyloid associated with Alzheimer’s disease become available to patients, we need to be able to determine whether a patient actually has these proteins in their brain and will benefit from the treatment. And if they don’t, we need to identify what disease they do have, which can be LATE.”
What is LATE?
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LATE is a newly characterized type of dementia that primarily affects individuals over 80 years old. Unlike AD,which is caused by the buildup of beta-amyloid and tau proteins,LATE is driven by the accumulation of TDP-43,a protein discovered by Breakthrough Prize-winning researchers at Penn Medicine.Autopsy studies reveal that LATE is remarkably common, with TDP-43 buildup present in 40% of adults over 80. Alarmingly, 55% of individuals with AD also exhibit LATE pathology.While both conditions cause memory loss, their cognitive profiles differ substantially. LATE predominantly affects memory, whereas AD impairs broader cognitive functions, such as executive functioning, planning, language, and visuospatial skills.
| Feature | LATE | Alzheimer’s Disease (AD) |
|—————————|—————————————|—————————————|
| primary Protein | TDP-43 | beta-amyloid and tau |
| Main Symptom | Memory loss | Memory loss + broader cognitive decline |
| Progression | Slower | Faster |
| Co-occurrence with AD | 55% of AD cases also have LATE | N/A |
Diagnosing LATE: A New Frontier
Currently, there is no test for TDP-43 buildup in living patients; its presence can only be confirmed post-mortem through brain autopsy. However, the new diagnostic criteria leverage cognitive evaluations, MRI scans to detect hippocampal atrophy, and tests for beta-amyloid and tau in cerebrospinal fluid and PET scans. These tools help differentiate LATE from other dementias, such as frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies.
In FTLD, patients experience executive function and language loss rather than memory impairment, and they do not exhibit hippocampal atrophy. In contrast, dementia with Lewy bodies is marked by motor dysfunction alongside cognitive decline.
Implications for Research and Treatment
The ability to accurately diagnose LATE opens doors for targeted research and therapy development. “Being able to accurately diagnose LATE in both forms sets the stage to engage in further, important research,” Dr. Wolk explained. “Not only can we use this diagnosis to develop clinical trials for TDP-43 drugs, but we can also investigate the efficacy of existing therapies on individuals with both LATE and AD, and potentially develop and test new therapies that target both diseases.”
this research, supported by the National Institutes of Health, represents a critical step forward in understanding and treating dementia. By distinguishing LATE from AD and other dementias, clinicians can provide more accurate prognoses and tailor treatments to individual patients, ultimately improving outcomes for this vulnerable population.
For more details on this groundbreaking research, visit the University of Pennsylvania.
Headline:
Unraveling LATE: A conversation with Dr. Emily Hartman on the New Diagnostic Guidelines for a Prevalent Form of Dementia
Introduction:
Join us as we delve into a groundbreaking development in dementia research with Dr. Emily Hartman, a renowned neurologist specializing in cognitive disorders. We discuss the newly established guidelines for diagnosing Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), a common yet under-recognized form of dementia, and its implications for patient care and treatment decisions.
What is LATE, and How Does it differ from Alzheimer’s Disease?
Dr. Hartman, could you start by explaining what LATE is and how it differs from Alzheimer’s disease, which is more commonly known?
Dr. Emily Hartman: ”LATE is a newly characterized type of dementia that primarily affects individuals over 80 years old. Unlike Alzheimer’s disease, which is caused by the buildup of beta-amyloid and tau proteins, LATE is driven by the accumulation of TDP-43, a protein discovered by researchers at Penn Medicine. While both conditions cause memory loss, their cognitive profiles differ substantially. LATE predominantly affects memory, whereas Alzheimer’s disease impairs broader cognitive functions, such as executive functioning, planning, language, and visuospatial skills.”
The Prevalence and Co-occurrence of LATE
That’s engaging.How prevalent is LATE, and can it co-occur with Alzheimer’s disease?
Dr. emily Hartman: “Autopsy studies reveal that LATE is remarkably common, with TDP-43 buildup present in 40% of adults over 80. Alarmingly, 55% of individuals with Alzheimer’s disease also exhibit LATE pathology. this co-occurrence highlights the importance of accurate diagnosis, as patients may not benefit from therapies targeting beta-amyloid and tau proteins if they primarily have LATE.”
Diagnosing LATE: A New Frontier
Until recently, there was no test for TDP-43 buildup in living patients.How have the new diagnostic criteria changed this landscape?
Dr. Emily Hartman: “The new diagnostic criteria leverage cognitive evaluations, MRI scans to detect hippocampal atrophy, and tests for beta-amyloid and tau in cerebrospinal fluid and PET scans. These tools help differentiate LATE from other dementias, such as frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies. In FTLD, patients experience executive function and language loss rather than memory impairment, and they do not exhibit hippocampal atrophy. In contrast, dementia with Lewy bodies is marked by motor dysfunction alongside cognitive decline.”
Implications for Research and Treatment
What are the implications of these new diagnostic guidelines for research and treatment?
Dr. Emily Hartman: “The ability to accurately diagnose LATE opens doors for targeted research and therapy development. We can now develop clinical trials for TDP-43 drugs and investigate the efficacy of existing therapies on individuals with both LATE and Alzheimer’s disease. Additionally, we can potentially develop and test new therapies that target both diseases. This research, supported by the National Institutes of Health, represents a critical step forward in understanding and treating dementia.”
Looking Ahead
Dr. Hartman, what are the next steps in LATE research, and how can the public stay informed about developments in this area?
Dr. Emily Hartman: “The next steps involve validating these diagnostic criteria thru larger-scale studies, identifying biomarkers for easier detection, and exploring potential therapies. The public can stay informed by following reputable sources such as the Alzheimer’s association, the National Institute on Aging, and research institutions like Penn Medicine. As we continue to unravel the mysteries of LATE,accurate diagnosis and targeted treatment will significantly improve outcomes for this vulnerable population.”
About Dr. Emily Hartman
Dr. Emily Hartman is a board-certified neurologist specializing in cognitive disorders and dementia. She serves as the Director of the Memory Disorders clinic at the University of Pennsylvania Health System and is an Associate professor of Neurology at the Perelman School of medicine. Dr.Hartman’s research focuses on the early detection and treatment of dementia, with a particular interest in Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).
We would like to thank Dr. Emily Hartman for her time and expertise in discussing this crucial development in dementia research.