A definitive diagnosis of Alzheimer’s is hard to obtain before death because only then can brain cells be scrutinized closely under the microscope.

So in living patients, doctors have to rely on various tests. From the information gathered they believe the diagnosis will be accurate for nearly all patients.

But on April 30, that all changed.

On that day a paper was published in the neurology journal Brain. It describes a new form of dementia that can mimic Alzheimer’s. The scientists believe as many as one patient in every five has been misdiagnosed. They don’t have Alzheimer’s disease, they suffer with LATE.

Mainly Affects the Over 80s

Using new and costly brain scans, studies reveal about a third of patients with Alzheimer’s symptoms don’t have the hallmark buildup of amyloid plaques. In other words, they don’t have Alzheimer’s.

But if not, then what do they have?

A large international team of scientists think they’ve come up with the answer. These patients have limbic-predominant age-related TDP-43 encephalopathy. That’s quite a mouthful, so it’s shortened to LATE.

TDP-43 is a protein that’s already well known to scientists. It’s been linked to Lou Gehrig’s disease and a form of dementia called frontotemporal lobar degeneration.

Yet, as lead researcher Pete Nelson from the University of Kentucky puts it, LATE “is a disease that’s 100 times more common than either of those, and nobody knows about it.”

In people with LATE, the protein is misfolded in the hippocampus, a key memory and learning center in the brain. But while it mimics Alzheimer’s, it usually only occurs in people over the age of 80, and their decline into dementia is slower. Both forms can occur at the same time.

Dr. Nelson is very excited about these new findings, saying, “We’re really overhauling the concept of what dementia is.

“We recently performed an autopsy on an individual diagnosed during life with Alzheimer’s. It turned out he didn’t have Alzheimer’s at all – he had LATE instead.

“Now that the scientific community is on the same page about LATE, further research into the ‘how’ and ‘why’ can help us develop disease-specific drugs that target the right patients.”

He thinks a third of people over 85 could have this disorder, and it also might explain the failure of drug trials for Alzheimer’s. They targeted the wrong protein — amyloid — in many of the patients that took part.

Positive Feedback

An observer who wasn’t involved in the study, Robert Howard, Professor of Old Age Psychiatry at the University College London, could hardly contain his enthusiasm:

“This is probably the most important paper to be published in the field of dementia in the last five years.

“LATE has clearly been an under-recognized contributor to dementia, particularly in people over the age of 80, and the paper will draw the attention of the field to this massively.

“It’s not often that I have a new and potentially useful diagnosis to share with my patients and colleagues, but I am sure that I will be introducing LATE to several of them over the next few weeks.”

Dr. James Pickett, Head of Research at Alzheimer’s Society UK, commented, “Though at an early stage, this research is taking a real step forward by proposing a new sub-type of dementia. This type of research is the first step towards more precise diagnosis and personalized treatment for dementia.”

Sandra Weintraub, a professor of neurology at Northwestern University Feinberg School of Medicine in Chicago, added, “TDP-43 likes certain parts of the brain that the Alzheimer’s pathology is less enamored of.

“This is an area that’s going to be really huge in the future. What are the individual vulnerabilities that cause the proteins to go to particular regions of the brain? It’s not just what the protein abnormality is, but where it is.”

While the feedback has been positive, it’s still a first step, as Dr Pickett points out. Dementia is diverse in character. Symptoms of different forms overlap, and multiple processes may be at work.

As one medic lamented, LATE “isn’t yet something doctors will be able to diagnose in the clinic.”


  1. https://www.ncbi.nlm.nih.gov/pubmed/31039256
  2. https://apnews.com/791c3ea82e1a40a59d603cfc109d1ad9
  3. https://edition.cnn.com/2019/04/30/health/dementia-late-alzheimers-study/index.html

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