Background: Alzheimer’s disease (AD) is the most seen cause of dementia. Biomarker
tests will be essential to improve the early diagnosis of AD, as treatment is more effective in the early
stage. The biomarkers of AD are divided into two main classes: amyloid β-peptide (Aβ) accumulation,
and tau-related neuronal degeneration. Peripheral blood represents an alternative sample for reflecting
pathological events occurring in the body. Blood samples are a possible alternative for cerebrovascular
fluid samples. The potential advantages of blood biomarkers are obvious: less invasive; simple to perform, convenient to
use, and not harmful to the patient.
Methods: Review publications about peripheral blood amyloid and tau biomarker tests by ELISA for AD stages; analyze
and interpret data in comparison with cerebrovascular fluid results. Also review publications about peripheral messenger
RNA biomarkers tests for AD diagnosis; analyze feasibility of diagnostic tests using blood messenger RNA biomarkers
Results: With sensitive and specific ELISA, extensive studies of plasma Aβ42 level and Aβ42/Aβ40 ratio were reported
during the development of blood-based protein biomarkers. High level of plasma Aβ42 increased risk of AD or cognitive
decline. The majority of the studies also indicated that increased plasma Aβ42 level was present prior to or at the start of
the development of AD, and Aβ42 level decreased as disease progressed; the lowest Aβ42/Aβ40 ratio reported was associated
with developing dementia. However, some studies showed inconsistent results. Reliable methods to determine levels
of tau and phosphorylated tau in blood of AD patients are still being explored.
Conclusion: The effort to discover and develop diagnostic protein biomarkers in blood has not led to feasible candidate
markers close to CSF. It may be helpful for each laboratory to set its own normal value or cut-offs due to different ELISA
kits used. Improving clinical diagnostic criteria may be another valuable option. Development of additional biomarkers
may also increase diagnostic accuracy. Compared with other technologies used in routine diagnostic tests, real time reverse
transcription polymerase chain reaction (RT-qPCR) is sensitive, specific, scalable, and cost-effective. There is relatively
less evidence of blood mRNAs acting as biomarkers in AD. The scientific merit and feasibility of diagnostic tests
for monitoring AD progress using blood mRNAs biomarker quantification need to be established.