The Perspective of Exosomal MicroRNAs as Biomarkers for Preclinical Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of aging-related irreversible dementia and a major unmet health concern. Mounting discoveries have documented the involvement of various molecular factors in AD pathogenesis and final neurodegeneration, in addition to two well-known pathological lesions in the brain, amyloid-β (Aβ) plaques and hyperphosphorylated tau (p-tau) tangles. Because of its complex multifactorial nature, AD pathology is not fully elucidated, accounting for the lack of disease-modifying therapies. Research on AD molecular mechanisms resulted, however, in the introduction of AD biomarkers to diagnostic practice based on the 2011 recommendations of the National Institute on Aging and Alzheimer’s Association ( 1 McKhann G.M. Knopman D.S. Chertkow H. Hyman B.T. Jack Jr., C.R. Kawas C.H. et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7: 263-269 Abstract Full Text Full Text PDF PubMed Scopus (8602) Google Scholar ). To support the assessment of dementia symptoms, Aβ and p-tau/tau are now assessed in the cerebrospinal fluid by immunoassays and in the brains of living patients using imaging methods. The use of these biomarkers led to the milestone discovery that molecular changes in AD precede by decades the onset of clinical symptoms of dementia. This finding revolutionized the concept of AD—the disease is defined as a biological continuum progressing gradually from a presymptomatic (preclinical) stage to mild, moderate, and severe dementia ( 2 Jack Jr., C.R. Bennett D.A. Blennow K. Carrillo M.C. Dunn B. Haeberlein S.B. et al. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018; 14: 535-562 Abstract Full Text Full Text PDF PubMed Scopus (3189) Google Scholar ). SEE CORRESPONDING ARTICLE ON PAGE 44 SEE CORRESPONDING ARTICLE ON PAGE 44 Exosomal MicroRNA-Based Predictive Model for Preclinical Alzheimer’s Disease: A Multicenter StudyBiological PsychiatryVol. 92Issue 1PreviewExosomal microRNAs (miRNAs) have been demonstrated to be biomarkers of Alzheimer’s disease (AD). However, whether exosomal miRNAs can predict AD at the asymptomatic stage remains unclear. Full-Text PDF