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A study comparing patients with early- and late-onset Alzheimer’s found more extensive tau deposits and accumulation at more than twice the rate in the early-onset group. The findings may help explain differences in symptoms and progression, but the study did not test treatments or establish why tau changes faster.
People with early-onset Alzheimer’s disease had more extensive brain deposits of tau and accumulated the protein at more than twice the rate of patients whose symptoms began at age 65 or later, according to a study published Nov. 4 in Science Translational Medicine. The results may help explain why early-onset disease can progress faster and involve symptoms beyond memory loss, but the research did not test treatments.
The researchers compared 390 people with early-onset Alzheimer’s from the Longitudinal Early-Onset Alzheimer’s Disease Study with 211 people with late-onset disease from the Alzheimer’s Disease Neuroimaging Initiative. The groups had average ages of 59 and 78, respectively. All participants had mild cognitive impairment or mild dementia due to Alzheimer’s and PET scans showing amyloid, an early disease biomarker.
A subset of participants received repeat tau PET scans over an average follow-up of two to three years, allowing researchers to track changes in tau. The study found more widespread tau in the early-onset group, and tau accumulation and spread were more strongly related to worsening memory in those patients, the study’s authors reported. The authors describe the work as the largest study to examine tau in early-onset Alzheimer’s against late-onset cases.
Among the early-onset participants, one in five had a presentation that was not primarily memory-related. By contrast, more than 99% of the late-onset patients with documented presentations had a memory-dominant form. Early-onset Alzheimer’s refers to symptoms beginning before age 65; the study excluded people with known disease-causing mutations.
How Faster Tau May Shape Symptoms
The findings add evidence that Alzheimer’s can differ by age of symptom onset, with tau differences more pronounced than amyloid differences in this study. Tau is a hallmark protein associated with Alzheimer’s, and its distribution through the brain may help explain why some younger patients experience changes in language, visual or spatial abilities, or executive functions such as planning and problem-solving, rather than memory problems at first.
That distinction matters for recognizing and studying the disease: a person with early-onset Alzheimer’s may initially struggle to interpret what they see, judge distances, find words, follow long sentences, or adapt to changing situations. These examples were described by co-senior author Renaud La Joie of the University of California, San Francisco. The study does not show that tau alone causes these symptoms, nor does it establish a new diagnostic test.
The results also raise questions for treatment research. The two drugs approved to slow Alzheimer’s progression target amyloid, while this study found larger differences between onset groups for tau. Senior author Gil Rabinovici said the results suggest tau-targeting approaches may warrant attention in early-onset disease and that younger patients could be considered for trials combining amyloid- and tau-targeting treatments. Those are research implications, not evidence that such treatments work better for this group.
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Study Groups and Tau Tracking
Early-onset Alzheimer’s accounts for about 5% of Alzheimer’s cases, according to the source report, and patients are more likely than older patients to have symptoms that are not initially dominated by memory loss. The study drew on two existing research cohorts rather than a single newly recruited sample. Their participants differed in average age and came from separate studies, a factor to keep in mind when interpreting comparisons.
Participants had evidence of amyloid on PET scans, and the repeat scans in a subset let researchers examine tau changes over time, not just compare deposits at one point. The study, titled “Distinct tau PET dynamics in early versus late age-of-onset Alzheimer’s disease,” was published in Science Translational Medicine and supported by the National Institute on Aging. Its focus was the pattern of tau, not the effectiveness of any Alzheimer’s medicine.
“We don’t fully understand why Alzheimer’s develops so early in some people.”
— Konstantinos Chiotis, first author and assistant professor at Karolinska Institutet
Why Tau Rises Faster Remains Unknown
The study shows an association between early age of onset and faster, more extensive tau accumulation, but it does not explain why the difference occurs. Researchers said it remains unclear whether genetic factors beyond known disease-causing mutations help drive the pattern. The study excluded people carrying such mutations, so its findings do not address that group.
It is also not clear whether the tau findings predict how an individual patient will progress or respond to a particular treatment. The study examined people with mild cognitive impairment or mild dementia and tracked tau in a subset over a limited follow-up period. It did not test medicines, compare treatment outcomes, or establish that tau-targeting therapies would slow early-onset disease.
Genetics and Treatment Trials Ahead
The researchers say further work is needed to determine what drives the differences in tau between younger- and older-onset disease, including whether other genetic factors are involved. That could help identify possible treatment targets, but no specific genetic explanation was established by this study.
The findings may also inform clinical trials testing therapies that target tau, alone or alongside amyloid-targeting drugs. Rabinovici suggested younger patients may be candidates for trials combining both approaches. Whether such trials will show a different benefit for early-onset patients remains an open question; the study itself provides no treatment results.
Key Questions
What did the study find about tau in early-onset Alzheimer’s?
The study reported more extensive tau deposits and accumulation at more than twice the rate in early-onset patients compared with late-onset patients.
How does the study define early-onset Alzheimer’s?
It refers to Alzheimer’s symptoms that begin before age 65. The comparison group had symptoms beginning at 65 or later.
Does the research show that tau treatments work better for younger patients?
No. The study tracked tau patterns but did not test treatments. Its authors said the results raise questions for future trials of tau-targeting or combined therapies.
What symptoms besides memory problems may occur?
Some early-onset patients may first have difficulties with language, visual or spatial abilities, attention, planning, or problem-solving, according to the study’s authors.
Why might tau accumulate faster in early-onset disease?
The reason is not known. Researchers said other genetic factors may contribute, but the study did not identify a cause.
Source: news-medical.net
