Fluid Candidate Biomarkers for Alzheimer's Disease: A Precision Medicine Approach.
Eleonora Del PreteMaria Francesca BeatinoNicole CampeseLinda GiampietriGabriele SicilianoRoberto CeravoloFilippo BaldacciPublished in: Journal of personalized medicine (2020)
A plethora of dynamic pathophysiological mechanisms underpins highly heterogeneous phenotypes in the field of dementia, particularly in Alzheimer's disease (AD). In such a faceted scenario, a biomarker-guided approach, through the implementation of specific fluid biomarkers individually reflecting distinct molecular pathways in the brain, may help establish a proper clinical diagnosis, even in its preclinical stages. Recently, ultrasensitive assays may detect different neurodegenerative mechanisms in blood earlier. ß-amyloid (Aß) peptides, phosphorylated-tau (p-tau), and neurofilament light chain (NFL) measured in blood are gaining momentum as candidate biomarkers for AD. P-tau is currently the more convincing plasma biomarker for the diagnostic workup of AD. The clinical role of plasma Aβ peptides should be better elucidated with further studies that also compare the accuracy of the different ultrasensitive techniques. Blood NFL is promising as a proxy of neurodegeneration process tout court. Protein misfolding amplification assays can accurately detect α-synuclein in cerebrospinal fluid (CSF), thus representing advancement in the pathologic stratification of AD. In CSF, neurogranin and YKL-40 are further candidate biomarkers tracking synaptic disruption and neuroinflammation, which are additional key pathophysiological pathways related to AD genesis. Advanced statistical analysis using clinical scores and biomarker data to bring together individuals with AD from large heterogeneous cohorts into consistent clusters may promote the discovery of pathophysiological causes and detection of tailored treatments.
Keyphrases
- cerebrospinal fluid
- high throughput
- gold nanoparticles
- label free
- cognitive decline
- healthcare
- quantum dots
- primary care
- traumatic brain injury
- mild cognitive impairment
- amino acid
- squamous cell carcinoma
- small molecule
- electronic health record
- single cell
- binding protein
- mesenchymal stem cells
- white matter
- resting state
- high resolution
- lymph node