Alzheimer’s or LATE? An Emerging Clinical Conundrum

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A brain disorder that mimics clinical features of Alzheimer’s dementia has been named and defined by an international consensus working group.

The newly-named pathology is called LATE (Limbic-predominant Age-related TDP-43 Encephalopathy), and was described in a consensus report by Peter Nelson, MD, PhD, of the Sanders-Brown Center on Aging at the University of Kentucky in Lexington, and colleagues, writing in Brain.

“LATE is a really important cause of dementia that has been understudied and underappreciated,” Nelson said.

“It’s been known for a while in the clinical pathology literature that as people get really old, there seems to be a dissociation between what we see — in terms of the neuropathology of Alzheimer’s — and cognitive impairments,” he noted in an interview with MedPage Today. “It turns out that there is not really a dissociation. There are a lot of people who don’t have Alzheimer’s but have impairments, and it turns out that many of these people have LATE.”

“In our autopsy cohort, for example, about a third of our patients — whether or not they had Alzheimer’s disease — also had TDP-43 proteinopathy,” Nelson said. “That means that a third of our patients had a substantial pathology for which there was no name.”

In Alzheimer’s clinical trials, many people also have LATE, he added. “If you treat them for Alzheimer’s disease and they don’t get better, does that mean the Alzheimer’s drug is not working? Not necessarily. We need to be able to remove these individuals from Alzheimer’s clinical trials, or we will never be able to get Alzheimer’s clinical trials to work,” Nelson said.

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