People diagnosed with Alzheimer's before age 65 often decline faster than older patients. New research may have uncovered one key reason why. A study, published in Science Translational Medicine, used advanced brain imaging to compare early-onset Alzheimer's disease (EOAD) with the more common late-onset form (LOAD).
Researchers found that younger patients had higher levels of tau, a protein closely linked to cognitive decline, and that the protein spread more rapidly through the brain over time. Tau forms abnormal tangles inside brain cells, disrupting communication between neurons and eventually causing them to die. While both early- and late-onset Alzheimer's are characterized by the buildup of amyloid plaques and tau tangles, the new findings suggest that tau pathology may be especially aggressive in younger patients.
"Younger patients can already have substantial tau pathology when symptoms are still mild, and the faster accumulation we observed suggests that further delays may be particularly consequential in this group," lead author Konstantinos Chiotis told Newsweek. "This helps explain the often more aggressive course of early-onset Alzheimer’s, although individual progression varies and cannot be predicted from the group averages in our study." Chiotis and colleagues analyzed tau PET scans from 390 people with early-onset Alzheimer's enrolled in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) and 211 people with late-onset Alzheimer's from the Alzheimer's Disease Neuroimaging Initiative. All participants had evidence of Alzheimer's-related amyloid buildup and either mild cognitive impairment or dementia.
At the start of the study, participants with early-onset Alzheimer's showed substantially higher tau levels across multiple brain regions than those with late-onset disease, even after researchers accounted for differences in cognitive impairment and amyloid burden. The tau deposits were also distributed more widely throughout the cortex, the outer layer of the brain involved in functions such as language, attention and problem-solving. Follow-up scans painted an even clearer picture.
Researchers found tau accumulated more quickly in younger patients, with the disease spreading across broader areas of the brain over time. Modeling suggested people with late-onset Alzheimer's took more than five additional years to reach comparable levels of tau buildup. The study also found a stronger relationship between tau levels and cognitive performance in younger patients.
In early-onset Alzheimer's, higher tau burden was more closely tied to worse scores on tests of memory and daily functioning, suggesting tau may be a more direct driver of symptoms in this group. Researchers believe these differences may help explain why people with early-onset Alzheimer's often present with atypical symptoms, including language, visual-processing or executive-function difficulties, rather than memory problems alone. Chiotis said these symptoms can sometimes be mistaken for conditions such as burnout or depression, potentially delaying diagnosis while the disease continues to develop.
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