Lymphocytes, Platelets, Erythrocytes, and Exosomes as Possible Biomarkers for Alzheimer's Disease Clinical Diagnosis.

In the aging world population, Alzheimer's disease accounts for more than 70% of all cases of dementia and is the sixth leading cause of death. The neurodegenerative processes of this disorder can begin 10-20 years before the clinical symptoms develop. Postmortem brain autopsy of Alzheimer's disease cases reveals characteristic hallmarks like extracellular amyloid plaques and intraneuronal neurofibrillary tangles and synaptic and neuronal disintegration with severe brain atrophy. Some studies have reported that platelets contain the amyloid protein precursor and the secretase enzymes required for the amyloidogenic processing of this protein. Thus, platelets can be a good blood cell-based marker to investigate the onset of Alzheimer's disease. Other studies have indicated cellular and molecular alterations in erythrocytes and lymphocytes from Alzheimer's disease subjects, which emphasize the systemic nature of the disorder. In addition, small extracellular vesicles called exosomes appear to be an important factor during the progression of the disease. These vesicles contain disease-associated molecules such as the amyloid protein precursor and tau protein. In this chapter, we will summarize the recent knowledge on the involvement of lymphocytes, erythrocytes, platelets, and exosomes in the development of Alzheimer's disease. The data will be reviewed with a view to applying the above elements as Alzheimer's disease early preclinical and late-stage biomarkers with potential use for clinical diagnosis, prognosis, and monitoring disease progression and treatment responses.