USC CiMUS and IDIS researchers unveil new advances in the approach to Alzheimer's-related diseases
- An international study coordinated by Pablo Aguiar from the Singular Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) of the USC and the Health Research Institute of Santiago de Compostela (IDIS), shows that people with primary age-related tauopathy (PART) do not always develop Alzheimer's disease, as science had previously maintained.
- The research suggests that this highly prevalent pathology in the ageing population, PART, requires a different therapeutic approach to Alzheimer's disease, and innovative PET imaging technology could be useful.
- The work has just been published in the prestigious journal JAMA Neurology.
Scientists have long known that when they encounter a patient with an abnormal accumulation of tau protein in the brain, together with the presence of amyloid plaques, they are looking at a diagnosis of Alzheimer's disease. However, some older people suffer from abnormal accumulation of this tau protein in the absence of amyloid plaques, a condition called primary age-related tauopathy (PART). Until now, several questions have been raised about this condition: will these patients eventually develop Alzheimer's disease, or is it a different pathology?
Now, international research coordinated by Pablo Aguiar from the CiMUS of the USC and IDIS has managed to answer this question and open up new therapeutic avenues for this highly prevalent neurodegenerative disease in the ageing population.
The research also involves Michael Schöll, from the University of Gothenburg (Sweden) and Michel Grothe, from the Institute of Biomedicine of Seville. In their publication in the journal JAMA Neurology, the scientists used positron emission tomography (PET) with a tracer sensitive to pathological tau to confirm that a significant number of people with cognitive impairment have PART. They showed that these patients continued to accumulate pathological tau over time, but at a much slower rate than people with Alzheimer's disease and in a restricted area of the brain.
The researchers conclude that, although this accumulation of tau in individuals with PART cannot strictly be considered a benign process, the evolution of the patients is completely different from Alzheimer's patients. Based on these results, PART and Alzheimer's disease probably represent two different pathological entities, each of which will require specific treatment. In this sense, tau PET, originally devised to detect tau in Alzheimer's disease, may have a new diagnostic utility in detecting patients with PART, for whom no diagnostic biomarker currently exists.
Image - PET detection of tau protein accumulation in the brain in patients with PART (left) and Alzheimer's disease (right).
To demonstrate this, co-lead authors Alejandro Costoya-Sánchez of the University of Santiago de Compostela and Alexis Moscoso of the University of Gothenburg analysed amyloid and tau PET images, magnetic resonance imaging, cerebrospinal fluid biomarkers, and neuropsychological test results from 965 people from three international studies: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Harvard Aging Brain Study (HABS) and the AVID-A05 study. Half were women, their average age was 74 years and 93% were Caucasian.
Of all participants, 264 patients had positive tau PET and negative amyloid PET, and were therefore classified as PART individuals, while 451 patients had positive tau PET and positive amyloid PET, and were classified as Alzheimer's patients. The remaining individuals showed negative biomarkers and were clinically cognitively healthy, and were therefore classified as controls.
The results of the comparison between these groups showed that, at baseline, people with Alzheimer's had widespread tau accumulation in the temporal, parietal and frontal lobes, while in the PART patients this accumulation was mainly limited to the medial temporal lobe. During the three years of follow-up, participants with PART accumulated little tau, and it was restricted to the temporal lobes. In contrast, people with Alzheimer's accumulated almost three times as much tau annually throughout the cerebral cortex.
The atrophy and cognitive impairment in these individuals reflected the effect of this tau accumulation. In patients with PART, atrophy was limited to the medial temporal lobe, with the rest of the cortex remaining intact, in contrast to Alzheimer's patients, who showed atrophy in other cortical regions beyond the temporal lobe. In addition, the cognitive impairment in individuals with PART was very mild, almost three times less than the impairment in Alzheimer's patients. The researchers were able to conclude that patients with PART show significantly slower rates of progression compared to Alzheimer's patients.
Since its publication, the work has had a significant impact among scientists globally, with editorials, comments and approaches of different kinds from experts from institutions such as the University of California, Berkeley, Stanford University School of Medicine and the University of Gothenburg itself on the scope of this work.
In conclusion, the results of this pioneering research suggest that PART appears to be a pathological entity distinct from Alzheimer's disease which, despite sharing some similar features, has different clinical and pathological consequences and therefore probably requires a different therapeutic approach. In this sense, tau PET may be a useful tool to detect patients with PART and to study the effect of new therapies focused on this pathology, which is so prevalent in the ageing population.
Link to the publication
Costoya-Sánchez A, Moscoso A, Silva-Rodríguez J, et al. Increased Medial Temporal Tau Positron Emission Tomography Uptake in the Absence of Amyloid-β Positivity. JAMA Neurol. 2023;80(10):1051–1061. doi:10.1001/jamaneurol.2023.2560
The Singular Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) of the University of Santiago de Compostela is part of the network of research centres with a new organisational and operational model, which constitutes the fundamental element of the R&D strategy of the CAMPUS VIDA project (Campus of International Excellence, MEC-MICINN, 2009). The mission of CiMUS is to carry out basic research of proven quality, with the aim of achieving advances in the prevention, understanding and treatment of chronic disease. The centre has been awarded CIGUS recognition by the Xunta de Galicia, which accredits the quality and impact of its research. More information on the website https://cimus.usc.gal/ or follow us on social media @cimususc (Twitter, Instagram and LinkedIn).