UW Medicine/Hand Crank Media
An international group of researchers have introduced new guidelines to diagnose LATE (Limbic-predominant age-related TDP-43 encephalopathy), a memory disorder often mistaken for Alzheimer’s disease because of the similarities in memory and thinking difficulties. LATE, both with and without co-occurring Alzheimer's pathology, affects over 10% of all individuals 65 years of age or older and about 25%–40% of those 85 years of age or older.
LATE is caused by a buildup of a protein called TDP-43. Because TDP-43 pathology can occur on its own, independent of Alzheimer’s pathology, and because it has a specific pattern of spread in the brain, researchers consider TDP-43 in older brains to be a distinct disease entity.
"With increasing availability of biomarkers enabling us to ascertain the presence of Alzheimer’s disease neuropathologic change during life, we will also be identifying progressive memory impairment in people who do NOT have Alzheimer’s disease," said Kimiko Domoto-Reilly, MD, MS, associate professor in neurology at UW Medicine, who is an author on a new paper in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
Back in 2019, when the results of the LATE consensus working group were published in the journal Brain, the term LATE was primarily used in research studies on TDP-43. In 2023, a group of experts convened to discuss the potential for clinical diagnostic guidelines for LATE. Now, an international research team provides the first clinical criteria for diagnosing LATE during life. This work, led by Penn Memory Center researchers, was supported, in part, by the UW Alzheimer's Disease Research Center.
Unlike the Alzheimer's proteins of beta-amyloid and tau, there is still no test for the presence of TDP-43 during life. TDP-43 can only be confirmed by brain autopsy after death. But in the new report, researchers share how they can get around this limitation. They are able to diagnose LATE during life by using cognitive evaluations, MRI scans, and testing for the presence of beta-amyloid and tau in cerebrospinal fluid and in PET scans of the brain.
"Having a specific alternative diagnosis can help patients and families to understand why the memory change is happening, and how to appropriately plan for the future," said Domoto-Reilly. "A comprehensive work up may provide insight into the rate of change: for example, if both LATE and Alzheimer’s disease are suspected, there may be more rapid change, whereas symptoms of LATE in isolation may progress fairly slowly."
These diagnostic criteria also help differentiate LATE from other types of dementia, like frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies. •
This research was supported by the National Institutes of Health (P30AG072979, R01 AG064233, P01 AG066597, R01AG034374, R01AG080667, K23AG062750, P30 AG066509).
