A new study from Sweden has provided further evidence that Alzheimer’s disease does not progress in the same way in every patient. Researchers at the Karolinska Institutet found that the distribution of the tau protein—a hallmark of Alzheimer’s disease—varies depending on whether symptoms begin before or after the age of 65. The findings were published in the European Journal of Nuclear Medicine and Molecular Imaging and may contribute to more individualised approaches to diagnosis and monitoring.
According to the World Health Organization (WHO), dementia affects approximately 57 million people worldwide, with Alzheimer’s disease accounting for around 60–70% of all cases. As the global population ages, improving the understanding of disease progression has become a major priority for neurological research.
Distinct patterns of tau accumulation
The Swedish investigation examined 57 participants, including individuals with mild cognitive impairment associated with Alzheimer’s disease, patients with dementia, and healthy volunteers. Researchers used tau positron emission tomography (PET) scans, magnetic resonance imaging (MRI), cognitive testing and blood analysis to compare biological changes between early-onset and late-onset Alzheimer’s disease.
The results suggested that patients whose symptoms developed before the age of 65 generally showed a broader spread of tau protein across the brain, extending into areas responsible for higher cognitive functions. In contrast, those with later-onset disease tended to exhibit a more localised pattern, with tau remaining concentrated within regions of the temporal lobe that are closely linked to memory.
The investigators also observed that even among people with mild cognitive impairment, some individuals with early-onset disease already displayed widespread tau deposition, indicating that biological progression may differ considerably between disease subtypes.
Blood biomarkers offer valuable—but incomplete—information
The study also evaluated p-tau217, a blood biomarker increasingly recognised for its role in detecting Alzheimer’s-related changes. Researchers reported that blood levels of p-tau217 generally increased as the disease became more advanced.
However, the findings demonstrated that blood measurements did not always accurately reflect the amount or distribution of tau protein detected within the brain using PET imaging. Some participants with relatively limited brain involvement still exhibited elevated blood biomarker levels, particularly among those with later-onset disease.
These observations suggest that while blood-based biomarkers provide important clinical information, they may not fully capture the complexity of pathological changes occurring throughout the brain.
Brain imaging remains closely linked to cognitive decline
Another important finding was the relationship between tau imaging and cognitive performance. PET scans showing greater accumulation of tau were more consistently associated with worsening memory and thinking abilities than blood biomarker measurements alone.
Researchers found particularly strong associations between tau accumulation in brain regions involved in memory processing—including the hippocampus, entorhinal cortex and amygdala—and declining cognitive function. In patients with early-onset Alzheimer’s disease, the relationship between widespread tau deposition and impaired cognition appeared especially pronounced.
Implications for future clinical care
The Swedish researchers suggest that combining blood biomarkers with advanced imaging techniques could improve the classification of Alzheimer’s disease and provide clinicians with a more complete picture of disease progression. Such an approach may also become increasingly valuable for evaluating the effectiveness of emerging disease-modifying therapies.
The authors emphasise, however, that the research involved a relatively small number of participants and represents a cross-sectional analysis rather than long-term follow-up. Larger studies will therefore be necessary to confirm these observations and determine how these biological differences influence disease progression over time.
Nevertheless, the findings reinforce growing evidence that Alzheimer’s disease is biologically heterogeneous and that personalised diagnostic strategies may play an increasingly important role in future neurological care.