Record TauPET Study Advances Alzheimer's Insights

"Such an extensive study of Alzheimer's disease has never been done before - in terms of both the number of participants or the wide geographical spread," says Rik Ossenkoppele, researcher in translational neuroscience at Lund University in Sweden and the Amsterdam University Medical Center.

Two proteins, beta-amyloid and tau, occur naturally in our brains and are crucially linked to Alzheimer's disease. If beta-amyloid accumulates and forms plaques between the nerve cells, it can disrupt communication. And if tau clumps together inside the nerve cells, it leads to the destruction of transport pathways and the cells die. It is at this stage, when tau begins to accumulate, that neurodegeneration and symptoms of cognitive impairment start being noticed.

In the study, the researchers analysed beta-amyloid and tau by using PET scans, an advanced form of imaging technology that can be used to measure Alzheimer-specific proteins in the brain. The 12,000 study participants come from 42 cohorts in Europe, Australia, North America and Asia, and have an average age of 70. Of the participants, about 7,400 were symptom-free, 2,200 had mild cognitive decline and around 1,500 had received a dementia diagnosis.

"Understanding how demographic, clinical and genetic factors relate to abnormal PET images is crucial for estimating the scope of the problem and how this can be used in clinical practice and research. A large, varied cohort is therefore important for being able to estimate how many people carry the pathological changes in the brain," says Oskar Hansson professor of neurology at Lund University.

Around two-thirds of those who develop Alzheimer's carry the genetic variant APOE ε4, which is the strongest known genetic risk factor for the disease. Individuals who carry the genetic variant, but who have not yet developed symptoms of the disease, start to accumulate amyloid and tau far younger than those who do not carry the variant. It is a matter of several decades, which suggests that disease-modifying medicines need to be introduced before symptoms manifest in these individuals.

Gender is another known risk factor for developing Alzheimer's - two out of three of those affected are women. One explanation is that the risk of women developing the disease increases when the protective effect of oestrogen disappears in connection with menopause. The immune system of women is also different from that of men, which may also be a contributory factor in the greater impact on women's brains. When the researchers compared women and men of the same age, abnormal tau accumulations were more prevalent among the women.

"The results of the study confirm previous research regarding risk factors such as APOE ε4 and gender, but due to the large number of study participants we can establish the results as highly reliable and provide highly robust prevalence estimates."

The information is important to enable clinics to identify populations that are more vulnerable to tau, which may also have consequences for inclusion in clinical trials. The next step is to examine which individuals within the cohorts develop symptomatic Alzheimer's disease over time and their prognoses.

"We also want to look at other factors that are linked to divergent PET results, such as race or ethnicity, level of education and unusual non-memory-related forms of Alzheimer's disease," says Rik Ossenkoppele