Early-Onset Alzheimer’s Shows Faster Tau Buildup, Study Finds

Patients with early-onset Alzheimer’s disease, whose symptoms begin before age 65, build up more extensive deposits of tau than patients whose symptoms start later, according to a new study. Tau accumulates at more than twice the rate in these younger patients compared with older ones and spreads more widely throughout the brain.

Experts say the findings may help explain why early-onset Alzheimer’s tends to progress faster and more often produces unusual symptom patterns affecting language, visual and spatial skills, and executive functioning, rather than memory loss alone.

The study, published in Science Translational Medicine, is reportedly the largest to examine tau in early-onset Alzheimer’s patients, who make up about 5% of all Alzheimer’s cases, compared with those whose disease began later in life.

According to co-senior author Renaud La Joie, “Patients with early-onset Alzheimer’s are more likely than older patients to present with symptoms unrelated to memory, at least initially.”

“They might have difficulty interpreting what they are seeing despite a normal eye exam. They might struggle with judging distances and may have trouble reading,” La Joie continued. “Some patients may experience a decline in language abilities in which they have difficulty retrieving words and following long sentences, although speech remains fluent. Others may struggle with executive functioning, such as attention, problem-solving, planning, and adapting to changing situations.”

The study drew on 390 early-onset patients from the Longitudinal Early-Onset Alzheimer’s Disease Study, average age 59, and 211 late-onset patients from the Alzheimer’s Disease Neuroimaging Initiative, average age 78. All had mild cognitive impairment or mild dementia from Alzheimer’s, confirmed by PET scans showing amyloid buildup, an early disease marker; a subset had repeat tau PET scans over two to three years, letting researchers track how tau changed over time.

Among early-onset patients, 1 in 5 had a presentation not dominated by memory problems, versus more than 99% of late-onset patients with documented presentations who showed the typical memory-first pattern.

First author Konstantinos Chiotis, said: “We don’t fully understand why Alzheimer’s develops so early in some people. A small minority carry a known disease-causing mutation, but these were excluded from our study. A key question is whether other genetic factors explain this more aggressive tau pathology. Understanding how genetics shape the differences we see in younger patients could reveal new treatment targets.”

Both drugs currently approved to slow Alzheimer’s target amyloid, yet the study found far bigger gaps between early- and late-onset disease in tau than in amyloid. Though the study didn’t test treatments, the results raise questions about how early-onset patients might respond to them.

Senior author Gil Rabinovici added that: “We found that tau accumulation and spread was particularly aggressive in patients with early-onset disease and was more strongly related to progression in memory loss.”

“Treatments that target tau may be particularly important in early-onset Alzheimer’s, and therefore younger patients may be good candidates for clinical trials combining treatments targeting both amyloid and tau.”