Fibrillar structures detected by AFM in the cerebrospinal fluid of patients affected by Alzheimer's disease and other neurological conditions

Alzheimer's disease (AD) is a progressive debilitating neurodegenerative disorder that is usually diagnosed after irreversible brain damage has occurred. The detection and morphological characterization of amyloid-β fibrils, which are predominantly implicated in the pathogenic process of the disease, in the cerebrospinal fluid (CSF), emphasized the significance of examining such biofluid. In this work the crude CSF samples collected from patients with Alzheimer's disease and with other neurological conditions were analyzed by atomic force microscopy (AFM). This approach allowed for the identification of peculiar fibrillar structures, exhibiting the regular repetition of dimeric globular units along the longitudinal axis, which share morphological similarities with fibrin protofibrils. Several studies have consistently shown that the disruption of the blood-brain barrier (BBB) and the infiltration of fibrinogen and components of the coagulation cascade are linked with a wide range of neurological diseases, including AD. Therefore, the role of the fibrillar structures we identified must be clarified, in order to ascertain if they contribute to the etiology of the disease, and their use as possible biomarkers of brain damage and disease progression should be assessed.