LATE (limbic-predominant age-related TDP-43 encephalopathy)

LATE is a brain disease that causes memory loss in very old age. Its full name is limbic-predominant age-related TDP-43 encephalopathy. It mostly affects people over 80, and its symptoms look a lot like Alzheimer's disease.¹

Experts gave LATE its name only in 2019, but it is not rare. Autopsy studies suggest it plays a part in memory loss for about 1 in 4 people who live into their late 80s.^1,3 Many people told they have Alzheimer's may have LATE instead, or both together. Knowing about it can help families understand a diagnosis that does not quite fit.

What is LATE?

Let's break down the long name:

• Limbic-predominant means it mostly affects the limbic system. These are deep brain areas that handle memory and emotion, such as the hippocampus (the brain's main center for forming new memories) and the amygdala.²
• Age-related means it is mainly a disease of very old age.¹
• TDP-43 is a protein that normally helps brain cells control their genes. In LATE, it folds the wrong way and forms clumps.¹
• Encephalopathy is a general word for a disease of the brain.

As the clumps spread, the memory areas lose brain cells and shrink.¹ Doctors who study brain tissue sort LATE into three stages. In stage 1, TDP-43 is found only in the amygdala. In stage 2, it has reached the hippocampus. In stage 3, it has also spread to part of the front of the brain.^2,3

Many people with LATE also have hippocampal sclerosis, meaning the hippocampus is badly scarred and shrunken. This is common in more severe LATE, but not everyone with LATE has it.²

How LATE is different from other TDP-43 diseases

TDP-43 also builds up in ALS (Lou Gehrig's disease) and in some kinds of frontotemporal dementia.¹ LATE is a different disease. It starts much later in life, it affects memory first, and it stays mostly in the memory areas.² Frontotemporal dementia usually starts younger and changes behavior or language first.

Who gets LATE, and how common is it?

Age is the strongest risk factor. LATE is uncommon before age 75 and becomes much more common in the 80s and 90s.⁴

Because LATE is confirmed only after death, most numbers come from brain donation studies:

• In autopsy studies of more than 6,000 people who died at an average age of 88, about 4 in 10 had TDP-43 clumps linked to LATE. About 1 in 4 had memory and thinking problems linked to it.¹
• Large community studies found LATE in more than 20%, and up to 50%, of people past age 80.²
• Among people 85 and older with memory loss, LATE is the main cause for about 1 in 5.⁴
• More than 1 in 10 people over 65 have some LATE changes in the brain.⁴

Genes play a part. Researchers have found risk genes, including APOE e4. This is the same gene form that raises the risk of Alzheimer's.^2,4 Genetic tests cannot tell LATE apart from Alzheimer's, so they are not used to diagnose it.⁴ Read more on genes and dementia.

Symptoms: why LATE looks like Alzheimer's

The symptoms of LATE are much like those of Alzheimer's:¹

• Trouble remembering recent events, conversations or where things are
• Trouble thinking things through and making decisions
• Trouble finding the right word
• Getting lost, even in familiar places

The memory problem has a typical pattern. A person may repeat back a list right away. But a short time later, they cannot recall it, and hints do not help much.⁴ This happens because the hippocampus cannot store new memories well.

In LATE, other skills often hold up fairly well for a long time. Language, attention and finding one's way may stay mostly intact until later stages.⁴ Some people have mild trouble naming things in a category, such as listing animals.⁴ Over many years, LATE can affect more areas of thinking and make daily tasks hard.³

How LATE changes over time

LATE alone usually moves slowly. Experts describe it as a slow memory decline that can stretch over many years.^3,4,5 Doctors suspect LATE when memory has been getting worse gradually for at least two years.⁴

LATE plus Alzheimer's often moves faster. The two often occur together. Just over half of people with LATE also have Alzheimer's brain changes.¹ Having both is linked to faster and more severe decline than having either one alone.^1,3,4 For more on having more than one cause, see mixed dementia.

How do doctors diagnose LATE?

For years, LATE could be confirmed only by looking at the brain after death. That is still true for a certain diagnosis.¹ In 2023, a federal research meeting noted there were no criteria for diagnosing LATE during life.⁵

In January 2025, a large group of experts published the first clinical criteria for LATE. These help doctors name it during life. The experts call them a starting point that still needs testing.⁴ The criteria apply to people with slowly worsening memory and clear shrinking of the hippocampus. They have two levels:⁴

Source for the table: Wolk and colleagues, 2025.⁴

Tests the doctor may use:

1. Memory and thinking tests to show the pattern of memory loss and which skills are spared. See memory and thinking tests.
2. An MRI scan to look for a hippocampus that has shrunk more than the rest of the brain. This is required for the criteria.⁴
3. Amyloid tests, such as an amyloid PET scan, a spinal fluid test or a blood test for Alzheimer's. These show whether Alzheimer's is present too.⁴
4. An FDG-PET scan (a scan that shows how the brain uses sugar) in some cases. A certain pattern can support LATE, but it is not required.⁴

Learn more about brain scans. A specialist, such as a neurologist or a doctor at a memory clinic, is most likely to know these criteria. See which specialist to see.

Is there a test for TDP-43 itself? Not yet. No proven blood, spinal fluid or PET test can measure TDP-43 in a living person.⁴ In late 2025, researchers reported that a very sensitive blood test found higher TDP-43 levels in people whose brains later showed advanced LATE. But the study included only 50 people, and it worked best in those who also had Alzheimer's.⁶ It is a research tool, not a test you can order.

Why the diagnosis matters for new Alzheimer's drugs

New drugs like lecanemab (Leqembi) and donanemab (Kisunla) remove amyloid from the brain. They are only for people with early Alzheimer's whose amyloid is confirmed by a test. They do not target TDP-43.

This matters in two ways:

• If amyloid tests are negative, the person cannot get these drugs. Some of these people may have LATE as the real cause of their memory loss.⁴ A name for the problem can still help with planning.
• If a person has both Alzheimer's and LATE, no one knows yet whether the anti-amyloid drugs work as well.⁴ Ask the doctor how possible LATE might change the expected benefit. Our page Are anti-amyloid treatments right for us? can help you prepare.

Researchers also think that people with LATE in past Alzheimer's drug studies may have made some drugs look less helpful than they were.³

Treatment and care

There is no medicine made to treat LATE yet.⁴ Researchers are working on ways to find it during life and on planning trials for LATE, both alone and with Alzheimer's.⁵

You may ask the doctor whether a memory medicine like donepezil is worth a try. These medicines were tested in Alzheimer's, not in LATE. Never start, stop or change a medicine on your own. Talk with your doctor or pharmacist first.

Most of what helps a person with LATE is the same care that helps with any memory loss:

Caregivers need support too. The Alzheimer's Association 24/7 Helpline at 800-272-3900 helps with any type of dementia. It offers interpreters in more than 200 languages.⁷ See caring for someone with dementia for more.

Joining research and brain donation

Much of what we know about LATE comes from people who joined research studies and donated their brains after death.¹ Researchers are now looking for ways to find LATE during life, including blood and spinal fluid tests.¹ If your family is interested, you can help. Ask about brain donation, a clinical trial, or a nearby Alzheimer's Disease Research Center funded by the National Institute on Aging.¹

Common questions

Is LATE a type of Alzheimer's disease?

No. LATE is caused by a different protein, TDP-43. Alzheimer's is caused by amyloid and tau. The two can look alike, and they often happen in the same person.¹

My mother's amyloid test was negative, but her memory is getting worse. Could it be LATE?

It could be, especially if she is over 75, her memory has declined slowly for years, and her MRI shows a shrunken hippocampus.⁴ Other causes are possible too, such as vascular dementia or treatable conditions. Ask her doctor whether "probable LATE" fits.

Should I worry if a relative had LATE?

LATE is mainly linked to very old age. Some genes raise the risk, but no genetic test can predict it.^2,4 Healthy habits and regular checkups are the best general steps for anyone.

Can LATE be found by a blood test?

Not yet. A blood test for TDP-43 is being studied, but it is not ready for use in clinics.⁶ Current blood tests for dementia look for Alzheimer's changes, not LATE.

When to get help

See a doctor soon if memory problems are new, are getting worse, or worry you. Memory loss in very old age is common, but it is not "just aging." Some causes, like low vitamin B12, thyroid problems or medicine side effects, can be treated. See treatable conditions that look like dementia and the first doctor visit about memory.

Education only. This page is general information written from the sources listed. It is not medical, legal or financial advice and does not replace a doctor, therapist or lawyer who knows your situation. How we write and check pages.