Around half of the people we thought had Alzheimer’s disease might actually have a recently-identified form of dementia. Researchers revealed their findings about limbic-predominant age-related TDP-43 encephalopathy, called LATE. This newly-discovered brain disorder mimics Alzheimer’s disease.
Now that scientists are learning to differentiate LATE from Alzheimer’s, the things they learned about the differences between the two forms of dementia could lead to breakthroughs in treating both conditions. Experts suggest that the reason so many drugs for Alzheimer’s fail in clinical trials is because many of the patients do not have Alzheimer’s – they have LATE.
The researchers developed diagnostic criteria for LATE, so doctors can distinguish the disease from Alzheimer’s. Alzheimer’s cases have baffled the medical community for many years. For example, some people who exhibited the clinical symptoms of Alzheimer’s did not respond to treatment. On autopsy, pathologists found the brains of these patients showed no signs of the disease. With the breakthrough of discovering LATE, doctors now think these patients probably had LATE, and not Alzheimer’s.
The Scope of the Situation
Over five million Americans over the age of 65 carry the diagnosis of dementia, with many of them currently identified as Alzheimer’s. There could be a couple of million people walking around with the wrong diagnosis, frustrated at the lack of hope because their condition does not respond to medication.
As many as half of all people older than 80 demonstrate some form of LATE in their brains on autopsy. About 25 percent of people over 80 show enough LATE involvement in the brain to impair their cognitive abilities and memory.
Distinguishing Between Alzheimer’s and LATE
People with LATE have a buildup of the protein TDP-43. We do not yet know much about TDP-43, except the protein is also present in amyotrophic lateral sclerosis (ALS), also called Lou Gehrig’s disease, and in frontotemporal lobar degeneration, another form of degeneration. In LATE patients, the TDP-43 spreads through the hippocampus and amygdala regions of the brain, areas that control memory.
Right now, we can only detect TDP-43 on autopsy of the brain, but scientists are currently working on developing a test that we can use on living patients to detect and measure TDP-43 levels. Researchers want to be able to measure a baseline level in young people and recheck the levels if the patient begins to show signs of dementia.
Alzheimer’s looks very different than LATE in the brain. Instead of having TDP-43, Alzheimer’s patients have a tau protein that combines with amyloid-beta plaques. We have imaging studies, like PET scans, that can find high levels of beta-amyloid. Patients with this finding usually have Alzheimer’s.
The tricky aspect of this issue is that some people have multiple forms of dementia. It is possible to have both LATE and Alzheimer’s. Since many of the signs of LATE look like Alzheimer’s, researchers are trying to develop objective tests that will distinguish the difference between LATE and Alzheimer’s. Scientists are also working on a “cocktail” of dementia drugs that patients can take to treat multiple forms of brain disorders at the same time, similar to HIV drugs that target more than one condition.
AARP. “Is It Alzheimer’s … or LATE?” (accessed June 20, 2019)