A new BBRC project investigates how blood pressure during sleep modifies Alzheimer’s risk

Dr Gonzalo Sánchez Benavides, researcher at the Barcelonaβeta Brain Research Center (BBRC), has obtained funding from the Spanish State Research Agency to develop the GLYMPH-AD project under the “Knowledge Generation Projects 2024” call of the Ministry of Science, Innovation and Universities. The study, designed in collaboration with Dr Mariateresa Buongiorno, an expert in glymphatic system function at Hospital Vall d’Hebron, will analyse how changes in blood pressure during sleep may affect the brain’s “cleaning” mechanisms and contribute to the risk of developing Alzheimer’s disease.

Under the title “Sleep blood pressure patterns, glymphatic failure and olfactory dysfunction in individuals at risk of Alzheimer’s disease (GLYMPH-AD)”, the project focuses on the study glymphatic system, a waste-clearance network that is particularly active during sleep. This system acts as a brain cleansing pathway that helps remove waste substances, including the beta-amyloid and tau proteins involved in Alzheimer’s disease. When this mechanism fails, these waste products can build up and promote the development of the disease.

The research will focus on cognitively unimpaired people but at increased risk of Alzheimer's disease, with particular attention to gender differences and changes related to menopause. Two hundred people from the ALFA+ longitudinal cohort, part of the ALFA (Alzheimer's and Families) cohort promoted by the “la Caixa” Foundation, will participate and undergo multimodal assessments throughout the project.

Over four years, and with funding of 123,750 euros, the team will examine the links between blood pressure patterns during sleep, glymphatic function and olfactory dysfunction, one of the earliest clinical signs described in Alzheimer’s disease. According to this hypothesis, the loss of the ability to detect odours could be an early sign that the glymphatic system is not working properly.

To address these questions, various advanced techniques will be combined, including 24-hour blood pressure monitoring to characterise nocturnal patterns in detail, smell tests to assess olfactory function, advanced magnetic resonance imaging to study brain structure and function, as well as cognitive assessments aimed at detecting subtle changes in memory and other functions. In addition, fluid and imaging biomarkers will be analysed, and genetic analyses will be carried out to precisely characterise risk and early biological changes related to Alzheimer’s disease.

“Normally, blood pressure falls during sleep, and it is known that when this does not happen, the risk of Alzheimer’s disease increases. However, the mechanism by which this occurs is unknown. Our hypothesis is that alterations in the nocturnal blood pressure pattern have an impact on the clearance of proteins such as amyloid, which are key to the biology of Alzheimer’s,” explains Dr Gonzalo Sánchez Benavides, who leads the project.

In the long term, the results of the project could help to design new preventive strategies, and sex-specific interventions, with the aim of delaying or preventing the onset of the disease.

The GLYMPH-AD project (code PID2024-163071OB-I00) is funded by MICIU/AEI/10.13039/501100011033 and the European Union, FEDER.