I just read about this.
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that was formally defined in 2019. It’s characterized by the abnormal accumulation of TDP-43 protein in the brain, particularly in limbic regions like the hippocampus and amygdala. This is the same protein that builds up with frontotemporal dementia and ALS.
LATE typically causes progressive memory loss and cognitive decline and resembles Alzheimer’s disease. It primarily affects people over 80 years old and becomes increasingly common with advanced age. On its own, it isn’t as bad as Alzheimer’s, but apparently it often is combined with Alzheimer’s, which makes it much worse.
Autopsy studies suggest LATE affects 20-50% of people over 80, making it one of the most common causes of dementia in the oldest old.
LATE tends to progress more slowly than typical Alzheimer’s disease, though the cognitive impact can still be substantial, especially when combined with other pathologies.The recognition of LATE as a distinct entity has important implications for understanding dementia in older adults and may help explain why some Alzheimer’s treatments haven’t been as effective in very elderly populations.
here is a paragraph from one of them:
LATE, or limbic-predominant age-related TDP-43 encephalopathy, is a relatively new dementia diagnosis. It first came to light roughly 20 years ago, after scientists observed that many people who died with Alzheimer’s symptoms had toxic clusters of the protein TDP-43 in their brains (sometimes in lieu of amyloid and tau, and sometimes in addition to them).
As the acronym suggests, LATE is most common in the later decades. Dr. Peter Nelson, a professor of pathology at the University of Kentucky College of Medicine, said that roughly a third of people in their 80s and 90s have signs of the disease in their brains.
As with Alzheimer’s, the part of the brain most affected is the hippocampus, and memory loss is the most common symptom. On its own, LATE progresses slowly and “is relatively benign,” Dr. Nelson said. But people often have both LATE and Alzheimer’s concurrently, which results in “a more swift and severe clinical course,” including anxiety, depression, hallucinations and delusions.
There isn’t a blood test for TDP-43, so doctors can only make a diagnosis based on a person’s symptoms and by ruling out other forms of dementia. The disease is most commonly discovered during an autopsy. The first clinical trial for a treatment for LATE is currently underway.
Links to the articles for those who can access:
https://www.nytimes.com/2025/12/01/well/mind/dementia-types-symptoms.html?smid=nytcore-ios-share
https://www.nytimes.com/2025/11/28/health/late-dementia-alzheimers.html?smid=nytcore-ios-share
I agree it is fascinating, but terrible.
I am wondering why these plaques or protein tangles build up in the brain. Is it similar to cholesterol that can form deposits in the arteries, with some people more at risk of earlier and more, also combined with environmental factors? What determines where the protein tangles form in the brain? And of course, can the formation of these protein tangles be reversed or prevented? I have read elsewhere that these processes are believed to start decades before symptoms appear, so I would think a cure would be almost impossible once symptoms manifest. But maybe prevention? If they could figure out what causes it and how it starts.
Is there information about how is it diagnosed? Is it only post-morten, like CTE?
Is there any treatment for it if diagnosed?
Thanks for the info.
Dementia is so fascinating and really when I first got into nursing in the late 60s there was only "senile". Then we became aware of the huge variety, what could be diagnosed before death with the newer MRI and what couldn't be diagnosed with certainty until autopsy. It is a fascination, but one you just hate to see on your doorstep. Oliver Sacks, who was so into the brain and its function, wrote throughout his lifetime with so much fascination about dementias and mental illnesses. The amount of discover over his lifetime regarding these conditions was enormous. And research keeps coming up with more.