Alzheimer’s disease (AD) is a progressive neurodegenerative disorder in which the pathophysiological processes can be triggered nearly 20 years before the decline in memory and cognitive abilities becomes noticeable. The misfolding and abnormal aggregation of β-amyloid (Aβ) and tau proteins in the brain are considered as the pathological hallmarks of AD. The early identification of individuals with this pathology is crucial for a successful treatment that can slow AD progression using existing behavioral and lifestyle changes as well as future chemo- and immunotherapies.
As an example of the key importance of nanoscale analytics, we demonstrate that protein aggregate morphology distinctly differs in both blood and cerebrospinal fluid (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). The importance of using label-free nanoscale analytics at the single-particle level is highlighted in our work conducted in collaboration with neurologists, which validates the diagnostics relevance of information obtained at nanometer-length scales and brings nanoscale analytics closer to clinical diagnosis of neurodegenerative diseases. 

Figure caption: Atomic force microscopy capable of operation in a liquid environment can be used to study protein aggregates directly in body fluid of patients at various stages of cognitive decline.