Contributions of Molecular and Optical Techniques to the Clinical Diagnosis of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These proteins are considered disease-specific biomarkers, and the definite diagnosis of AD relies on their post-mortem identification in the brain. The clinical diagnosis of AD is challenging, especially in the early stages. The disease is highly heterogeneous in terms of clinical presentation and neuropathological features. This phenotypic variability seems to be partially due to the presence of distinct Aβ conformers, referred to as strains. With the development of an innovative technique named Real-Time Quaking-Induced Conversion (RT-QuIC), traces of Aβ strains were found in the cerebrospinal fluid of AD patients. Emerging evidence suggests that different conformers may transmit their strain signature to the RT-QuIC reaction products. In this review, we describe the current challenges for the clinical diagnosis of AD and describe how the RT-QuIC products could be analyzed by a surface-enhanced Raman spectroscopy (SERS)-based systems to reveal the presence of strain signatures, eventually leading to early diagnosis of AD with the recognition of individual disease phenotype.