Lighthouses are used to warn ships not to crash inland. Virgil was sent in to guide Dante through Hell. Marge Simpson, Homer’s better half oversees him through any conceivable shenanigans. As that, biomarkers points us for normal biological and pathological processes that are often exhaustively evaluated, measured and updated.
Alzheimer’s Disease (AD) is a degenerative brain disease and claims the throne for the cause of dementia. Symptoms highlighted are incapacitated memory, language, and cognitive skills, thus culminating in behavioural changes and lack of judgement thereof.
The early biomarkers of AD were Positron Emission Tomography (PET) and Cerebrospinal fluid (CSF), but a dark cloud rule over the duo: financial and logistics limitation. A new candidate marker was asked for; blood-based AD marker answered.
Hence this read spells the network of international, interdisciplinary groups to assess the present landscape of blood-based biomarkers, besides engineering to-be biomarker research (cascading from identification, assay development and finally to clinical validation).
Blood-based biomarkers are turning a few heads to its direction for they are economical, less invasive (does not necessitate a lumbar puncture, as CSF demands it). Blood testing is an established clinical routine everywhere, what more the ease to perform it - at a repeated interval. Mature blood sample-handling infrastructures for collection and process with the existing system exist, thus qualifying for primary care settings and population-based. Last but surely not the least, blood-based biomarkers could offer pathophysiology biomarkers candidate.
The challenges thrown at for biomarkers’ development are a plethora of candidate biomarkers - from protein concentration all the way to metabolic products; ergo variability in the analysis after.
Besides that, potential biomarkers may have a lame concentration in blood, a glaring overlap of neurodegenerative diseases and other co-occurring secondary diseases in AD patients, effectively muddling the plasma’s protein profile. On the rapid fly-by, other factors to look into are blood-brain barrier (biomarkers must cross it!); active v. passive transport; and finally, concentration difference.
Civilizations are not built in a single week. Anything that suggests otherwise must be treated with eyebrows raised high.
With that nuance, another facade of the development was the assay reliability, healthy replication and initial result validation; insensitive established immunochemical methods, inconsistent clinical cohort studies, samples’ availability, pre- and analytical differences, whilst the protocol for the former is in shambles.
Excellent ideal biomarker attributions are fitting into the context of use (COU), capable of ruling out other neurodegenerative diseases’ symptom resembling AD, a predictive accuracy for screening tools, diagnostics resources and costs depends on COU. The seal of finality - capable of delivering high positive predictive value (PPV).
Blood-based biomarkers is a holy grail (metaphorically). It helps to decide who is delegated to which specialist. Precision medicine will no longer be as dream abides - for it will improve clinical outcomes and patients care, all the while placing a brick to build large biological databases and high throughput ‘omics’ studies. A disconnect between relevant actors (academia, regulatory bodies, and industry) shall be no more to advance the goal.
A lighthouse called biomarker,
Beacon the ships to harbour,
Whence, the congregation of all that is good.
Watch the video below for a better hear of biomarkers.
Sources: Nature Review, Science Direct, Nature.com
