The brain and its health are essential for our (physical mental, social, and spiritual) wellbeing, for being able to realize our potential as individuals, and also for a fair, well-functioning, and productive society. However, today the world is facing a healthcare crisis related to the very high (and increasing) burden of brain disorders. As a response to this crisis, the “Swiss Brain Health Plan” (SBHP) was conceptualized in the context of other initiatives launched to value, promote, and protect brain health over the entire life course. In the first section of this position paper, the following fundamental considerations of the SBHP are discussed: (1) the high (and increasing) burden of brain disorders in terms of prevalence (>50% of the population suffers from a brain disorder), disability, mortality, and costs; (2) the prevention of brain disorders; (3) the operational definition of brain health; (4) determinants of brain health; (5) international initiatives to promote brain (including mental) health including the World Health Organization (WHO) intersectorial global action plan on epilepsy and other neurological disorders (NDs) (IGAP) and the WHO comprehensive mental health action plan. In the second section of the paper, the five strategic objectives of the SBHP, which has the vision of promoting brain health for all across the entire life course, are presented: (1) to raise awareness; (2) strengthen cross-disciplinary and interprofessional training/educational programs for healthcare professionals; (3) foster research on brain health determinants and individualized prevention of brain disorders; (4) prioritize a holistic (non-disease-specific), integrated, person-centered public health approach to promote brain health and prevent brain disorders through collaborations across scientific, health care, commercial, societal and governmental stakeholders and insurance providers; (5) support, empower, and engage patients, caregivers, and patient organizations, and reduce the stigma and discrimination related to brain disorders. In the third section of the paper, the first (2024) steps in the implementation of the SHBP, which will be officially launched in Zurich on 22 November 2023, are presented: (1) a definition of the overall organization, governance, specific targets, and action areas of the SBHP; (2) the patronage and/or co-organization of events on such specific topics as brain research (Lausanne), dementia (Geneva), stroke (Basel), neurohumanities (Bellinzona), sleep (Lugano), and psychiatry (Zurich); (3) the conduction of a new study on the global burden of brain disorders in Switzerland; (4) the launching of an international Certificate of Advanced Studies (CAS) on Brain Health at the University of Bern. In the fourth section of the paper, there is a concise executive summary of the SBHP.

Identifying blood-based physical biomarkers for detection of Alzheimer’s disease.

Alzheimer’s disease (AD) associated proteins exist in cerebrospinal fluid (CSF). This paper evidences that protein aggregate morphology distinctly differs in CSF of patients with AD dementia (ADD), mild cognitive impairment due to AD (MCI AD), with subjective cognitive decline without amyloid pathology (SCD) and with non-AD MCI using liquid-based atomic force microscopy (AFM). Spherical-shaped particles and nodular-shaped protofibrils were present in the CSF of SCD patients, whereas CSF of ADD patients abundantly contained elongated mature fibrils. Quantitative analysis of AFM topographs confirms fibril length is higher in CSF of ADD than in MCI AD and lowest in SCD and non-AD dementia patients. CSF fibril length is inversely correlated with CSF amyloid beta (Aβ) 42/40 ratio and CSF p-tau protein levels (obtained from biochemical assays) to predict amyloid and tau pathology with an accuracy of 94% and 82%, respectively, thus identifying ultralong protein fibrils in CSF as a possible signature of AD pathology.

Neurodegenerative diseases like Alzheimer’s disease are characterized by the accumulation of misfolded proteins into fibrils in the brain. Atomic force microscopy is a nanoscale imaging technique that can be used to resolve and quantify protein aggregates from oligomers to fibrils. Recently, we characterized protein fibrillar aggregates adsorbed on the surface of red blood cells with atomic force microscopy from patients with neurocognitive disorders, suggesting a novel Alzheimer’s disease biomarker. However, the age association of fibril deposits on red blood cells has not yet been studied in detail in healthy adults. Here, we used atomic force microscopy to visualize and quantify fibril coverage on red blood cells in 50 healthy adults and 37 memory clinic patients. Fibrillar protein deposits sporadically appeared in healthy individuals but were much more prevalent in patients with neurodegenerative disease, especially those with Alzheimer’s disease as confirmed by positive CSF amyloid beta 1–42/1–40 ratios. The prevalence of fibrils on the red blood cell surface did not significantly correlate with age in either healthy individuals or Alzheimer’s disease patients. The overlap in fibril prevalence on red blood cells between Alzheimer’s disease and amyloid-negative patients suggests that fibril deposition on red blood cells could occur in various neurodegenerative diseases. Quantifying red blood cell protein fibril morphology and prevalence on red blood cells could serve as a sensitive biomarker for neurodegeneration, distinguishing between healthy individuals and those with neurodegenerative diseases. Future studies that combine atomic force microscopy with immunofluorescence techniques in larger-scale studies could further identify the chemical nature of these fibrils, paving the way for a comprehensive, non-invasive biomarker platform for neurodegenerative diseases.