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

  • Urszula Wojda
    Correspondence
    Address correspondence to Urszula Wojda, Ph.D.
    Affiliations
    Laboratory of Preclinical Testing of Higher Standard, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
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      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 (
      • 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.
      ). 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 (
      • 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.
      ).
      SEE CORRESPONDING ARTICLE ON PAGE 44
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