When a parent or grandparent begins forgetting names, misplacing objects or repeating the same stories, the diagnosis most people expect is Alzheimer’s disease. For decades, Alzheimer’s has dominated public understanding of dementia, becoming almost shorthand for memory loss itself.
But that assumption is increasingly being challenged. Neurologists now know that a significant number of people with Alzheimer’s-like symptoms actually have a different condition altogether – one that most families, and even many doctors, have only recently heard of.
Short for limbic-predominant age-related TDP-43 encephalopathy, LATE appears to account for around 15–20 per cent of all dementia cases, and may affect up to 1 in 3 people over the age of 85.
Having been officially defined in 2019, formal clinical guidelines for identifying it in living patients were only published last year.
“We didn’t know how common it was until we started to get biomarker tests for people,” says Dr Andrew Budson, chief of cognitive behavioural neurology at the Veterans Affairs Boston Healthcare System and a professor of neurology at Boston University.
“All of a sudden, it was clear there were lots of people that we thought had Alzheimer’s who didn’t, even though clinically they were virtually identical.”
The growing distinction is changing what a dementia diagnosis can mean. If an older relative’s memory loss is caused by LATE rather than Alzheimer’s, decline may be slower and more narrowly focused.
How doctors tell the difference – and how it could change treatment – is now a central question.
What are the symptoms of LATE?
The hallmark of LATE is progressive memory loss, particularly difficulties remembering recent events – what neuroscientists call episodic memory. People may struggle to recall conversations, appointments or television programmes they watched the night before.
As the disease advances, language can also be affected. Word-finding becomes harder, and some people begin to lose the meaning of familiar words altogether.
Budson recalls one patient who could no longer remember what “charades” meant, and later became confused about what a pumpkin was. “It’s as if they grew up in a culture that just didn’t have pumpkins,” he says.
Later still, subtle behavioural changes can emerge. “When it begins to affect the lower part of the frontal lobe, there can be some behavioural disturbances,” Budson explains.
“Not major, but people may become a little bit disinhibited – saying or doing things that we would think are socially inappropriate, like commenting on someone’s physical appearance.”
One important difference from Alzheimer’s is tempo. LATE generally develops later in life – typically in people in their late 70s, 80s and beyond – and tends to progress more slowly.
Many individuals experience years of relatively isolated memory loss before other thinking skills become noticeably affected.
“People often have years of slowly progressive memory loss without other significant symptoms with LATE,” says Dr David Wolk, professor of neurology at the University of Pennsylvania. That slower trajectory can make an enormous difference to the quality of life and long-term planning for families.
Another complicating factor is that LATE frequently overlaps with Alzheimer’s itself. Up to half of people with LATE also show Alzheimer’s pathology in their brains, Wolk says, and when the two conditions coexist, decline can be faster and more severe.
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LATE, Alzheimer’s and normal ageing – what’s the difference?
Distinguishing early dementia from normal age-related forgetfulness is notoriously difficult. Many healthy older adults notice that names come more slowly, that they need reminders, or that multitasking feels harder than it once did.
The key difference lies in what happens to the memory itself. In normal ageing, Wolk explains, the problem is usually retrieval – accessing information that is still stored correctly. With a prompt or cue, people can often recognise or recall what they had forgotten.
In LATE and Alzheimer’s, by contrast, the memory trace itself may be lost.
Budson offers a useful analogy. Think of your memory as a filing system. The frontal lobes act like a filing clerk, collecting information from the world and deciding where to store it. The hippocampus is the filing cabinet where those records are kept.
In normal ageing, the clerk becomes less efficient. Information may need to be repeated, retrieval takes longer, and hints help jog recall. But if the information made it into the cabinet in the first place, it should still be there.
In Alzheimer’s and LATE, the cabinet itself is damaged. “You can have the best, most efficient clerk in the world, pulling in information from the outside world,” Budson says, “but that information is just disappearing down a hole, never to be recovered again.”
Where LATE diverges from Alzheimer’s is in breadth and speed. Alzheimer’s typically spreads more rapidly through multiple brain networks, affecting planning, problem solving, spatial awareness and language alongside memory. LATE tends to remain more narrowly focused on memory for longer, and progresses more slowly overall.
Pathologically, the two diseases are also defined by different proteins. Alzheimer’s is marked by the accumulation of amyloid-beta plaques and tau tangles. LATE is driven by TDP-43. This distinction is becoming increasingly important as new drugs target specific biological pathways.
What causes LATE?
At its core, LATE is a disease of misbehaving proteins. In healthy brain cells, proteins help neurons maintain their structure and carry out vital functions. In LATE, a protein called TDP-43 begins to clump together inside neurons. These accumulations injure cells and eventually lead to their death.
This same protein was first linked to amyotrophic lateral sclerosis (ALS) and a form of frontotemporal dementia around two decades ago. Only later did researchers realise that TDP-43 commonly appears in much older brains, producing a pattern of memory loss distinct enough to justify its own diagnosis.
The regions most affected overlap heavily with those damaged in Alzheimer’s disease.
“There are three main structures that get affected by LATE,” Budson explains. “The first is the hippocampus; the second is the outer part of the temporal lobe; and then the base of the frontal lobe as well.”
Each of these areas plays a different role in cognition. The hippocampus helps us form new memories, such as recalling a recent conversation or what we ate for breakfast. Parts of the temporal lobe support language and meaning – allowing us to recognise words and objects. The underside of the frontal lobes contributes to behaviour, impulse control and aspects of working memory.
Because the same memory circuits are involved in Alzheimer’s, the two conditions can look remarkably similar, especially early on.
Can doctors diagnose LATE during life?
Until recently, LATE could only be confirmed after death, when pathologists could directly examine brain tissue. That remains the gold standard. However, clinicians can increasingly make a strong suspicion of LATE during life by combining cognitive testing with biomarker evidence.
“If biomarker tests or Alzheimer’s scans are negative, then I say, ‘OK, this is probably LATE,’” Budson says.
In other words, if someone has Alzheimer’s-like memory problems but tests show no evidence of amyloid or tau – the signature proteins of Alzheimer’s – LATE becomes a leading possibility.
For patients and families, one of the most pressing questions is whether knowing a diagnosis of LATE alters treatment.
The answer is nuanced. Newer disease-modifying Alzheimer’s drugs are designed specifically to target amyloid biology. These medicines are not expected to benefit people whose primary problem is LATE rather than Alzheimer’s.
However, older Alzheimer’s medications that boost acetylcholine – a neurotransmitter involved in memory and attention – are often reasonable to try. “There is some evidence that this neurotransmitter is also reduced in LATE,” Wolk says.
Budson is keen to reassure patients not to abandon treatments prematurely. “I’m 100 per cent sure that lots of people with LATE were in those clinical trials that led to the approval of these drugs,” he says.
“I don’t want either the patient or the doctor to think treatment should be stopped just because the person doesn’t have Alzheimer’s. It almost certainly will benefit people with LATE as well.”
At present, there are no treatments that specifically target TDP-43 in LATE, although one clinical trial is underway. Insights from ALS and frontotemporal dementia research may eventually translate across, according to Wolk.
You might think distinguishing between different types of dementia mattered little, because treatments were limited and outcomes similar.
Yet from a practical standpoint, prognosis matters. Knowing that LATE typically progresses more slowly and remains memory-focused for longer can help families plan care, maintain independence where possible, and set realistic expectations.
From a scientific perspective, accurate diagnosis is essential. Mixing different diseases together in clinical trials makes it harder to detect whether a treatment truly works.
There is also a public-health dimension. As populations age, conditions that primarily affect the very old will become increasingly common.
“LATE is a really widespread condition, and it is so slow-moving that it may account for some aspects of age-associated cognitive decline before it progresses to the point where it is beyond normal ageing,” Wolk says. “Given how prevalent it is, it is also of major public health interest as our society continues to live longer.”
And while LATE does not come with the dramatic public profile of Alzheimer’s, for many families, it may already be shaping their experience of ageing and memory loss.
Budson offers a candid perspective. “LATE progresses slowly and tends to affect people later in life,” he says. “So the hopeful message is that many people will not have a lot of progression before they die of other causes. I don’t know if that’s a comforting thought – but I think it is realistic.”
What LATE ultimately reveals is how much nuance there is hidden inside the label ‘dementia’. Two people can arrive at the same symptoms by very different biological routes, with different speeds of decline, different risks, and potentially different responses to treatment.
For patients and families, that distinction may not always change day-to-day care. But as tools for diagnosis improve, it increasingly shapes how clinicians predict what lies ahead, how researchers design trials and where future therapies are likely to emerge.
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