A multilateral collaboration led by the Barcelonaβeta Brain Research Center (BBRC), a research center of the Pasqual Maragall Foundation, has managed to measure, thanks to a new, especially sensitive Magnetic Resonance Imaging (MRI) sequence, a decrease in cerebral blood flow in the early stages of Alzheimer’s disease, before clinical symptoms appear. Experts in the development of new MRI sequences, clinical professionals from Hospital del Mar and other collaborators have participated in this project, which has provided cutting-edge biomarkers for Alzheimer’s disease.
The team used an innovative technique called Time-encoded Arterial Spin Labeling (teASL) to detect very early changes in the brain blood flow of the study participants. The results, published in the journal Alzheimer’s & Dementia, reveal that people with Alzheimer’s disease show reduced blood flow in specific areas of the brain also during the early stages of the disease.
Alzheimer’s disease is a progressive neurodegenerative pathology and is the leading cause of dementia. It is distinguished by the presence of two types of pathology: amyloid beta (Aβ), which can be found in cognitively healthy individuals long before the onset of clinical symptoms; and tau pathology, which closely precedes neurodegeneration and cognitive and functional decline. Aβ and tau pathologies can be detected in vivo by fluid biomarkers, such as cerebrospinal fluid and blood, as well as by positron emission tomography (PET) imaging. Furthermore, biomarkers of synaptic dysfunction and neurodegeneration are altered in cognitively healthy individuals with abnormal Alzheimer’s biomarkers.
One of the first processes activated in the brain by Alzheimer’s disease, characterized by the accumulation of beta amyloid and tau proteins, is the reduction of cerebral blood flow. This flow is crucial, as it provides oxygen and glucose to the brain, and it is essential to maintain it within normal levels to ensure the health and proper functioning of this organ. Alterations in cerebral blood flow can precede or accompany various neurological conditions, including Alzheimer’s disease. Therefore, measuring it accurately is essential to understand these conditions.
In fact, the cerebral blood flow (CBF) is decreased in patients with Alzheimer’s disease who present cognitive impairment compared to healthy controls. However, the magnitude of the reduction in CBF in individuals with Alzheimer’s who have altered biomarkers of beta amyloid (Aβ+) is a matter of debate. Cerebral blood flow can be measured using different techniques, such as single-photon emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) with arterial spin labeling (ASL), although they have different costs and safety profiles, and some limitations..
Dr Michalis Kassinopoulos, a postdoctoral researcher at the BBRC and one of the lead authors of the study, explains: “Until now, available ASL techniques allowed us to measure and compare cerebral blood flow in people using ‘single delay time’. This refers to the time it takes for arterial blood to transit from the carotid arteries (where it is ‘labeled’) to the brain region of interest (known as arterial traffic time).”
Through a research collaboration with Philips, the BBRC has had access to a new ASL MRI sequence developed by Leiden University Medical Center, known as time-encoded ASL (teASL). This more sensitive and accurate tool improves the estimation of cerebral blood flow by reducing differences in arterial transit time. The researchers have used teASL to measure cerebral blood flow and explore its relationship with amyloid and tau pathology, both linked to Alzheimer’s disease. In addition, the team has studied how decreased cerebral blood flow relates to cerebrospinal fluid biomarkers associated with synaptic dysfunction and neurodegeneration, as well as cognitive performance. This study has shown, for the first time in asymptomatic individuals, that cerebral blood flow levels are associated with markers of tau pathophysiology, synaptic dysfunction and neurodegeneration.
Useful measurement for defining future Alzheimer’s prevention strategies
For this study, a total of 59 participants were divided into three groups: the “control” group, with 24 healthy participants without cognitive impairment or amyloid protein accumulation in the brain; 18 healthy volunteers without cognitive impairment but with amyloid pathology present, and 17 patients from the Medical Research Unit of the Hospital del Mar in Barcelona, affected by the disease. Of the healthy participants, thirty belong to the Alfa study, promoted by the “la Caixa” Foundation.
Reduced cerebral blood flow is not only present in people in asymptomatic stages of Alzheimer’s, but also in people experiencing cognitive decline with beta-amyloid pathology.
The study shows that reduced cerebral blood flow is not only present in people with asymptomatic stages of Alzheimer’s, but also in people experiencing cognitive decline with beta-amyloid pathology. “Reduced blood flow is an earlier event in the pathological cascade than previously thought, spanning preclinical stages,” said Dr Juan Domingo Gispert, BBRC collaborator and corresponding author of the study. “These findings provide insight into the role of this early process in the disease and may help shape future prevention strategies,” he concluded.
Source: Pasqual Maragall Foundation
