, Volume 14, Issue 1, pp 35–53

Biomarkers for the Early Detection and Progression of Alzheimer’s Disease

  • Scott E. Counts
  • Milos D. Ikonomovic
  • Natosha Mercado
  • Irving E. Vega
  • Elliott J. Mufson

DOI: 10.1007/s13311-016-0481-z

Cite this article as:
Counts, S.E., Ikonomovic, M.D., Mercado, N. et al. Neurotherapeutics (2017) 14: 35. doi:10.1007/s13311-016-0481-z


The recent failures of potential disease-modifying drugs for Alzheimer’s disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible. In this regard, positive amyloid or tau tracer retention on positron emission tomography imaging, low CSF concentrations of the amyloid-β 1-42 peptide, high CSF concentrations in total tau and phospho-tau, mesial temporal lobe atrophy on magnetic resonance imaging, and temporoparietal/precuneus hypometabolism or hypoperfusion on 18F-fluorodeoxyglucose positron emission tomography have all emerged as biomarkers for the progression to AD. However, the ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD. This review highlights advancements in biological fluid and imaging biomarkers that are moving the field towards achieving the goal of a preclinical detection of AD.


Alzheimer’s disease Mild cognitive impairment Biomarker Cerebrospinal fluid Positron emission tomography Amyloid 

Supplementary material

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Funding information

Funder NameGrant NumberFunding Note
National Institute on Aging
  • AG043375
  • AG026032
National Intitute on Aging
  • AG042146
BNI Barrow and Beyond
    Saint Mary’s Foundation
      Miles for Memories of Battle Creek
        National Insitute of Aging
        • PO1AG025204

        Copyright information

        © The American Society for Experimental NeuroTherapeutics, Inc. 2016

        Authors and Affiliations

        • Scott E. Counts
          • 1
          • 2
          • 3
        • Milos D. Ikonomovic
          • 4
          • 5
          • 6
        • Natosha Mercado
          • 1
        • Irving E. Vega
          • 1
        • Elliott J. Mufson
          • 7
        1. 1.Department of Translational Science and Molecular MedicineMichigan State UniversityGrand RapidsUSA
        2. 2.Department of Family MedicineMichigan State UniversityGrand RapidsUSA
        3. 3.Hauenstein Neuroscience CenterMercy Health Saint Mary’s HospitalGrand RapidsUSA
        4. 4.Department of NeurologyUniversity of PittsburghPittsburghUSA
        5. 5.Department of PsychiatryUniversity of PittsburghPittsburghUSA
        6. 6.Geriatric Research Education and Clinical CenterVA Pittsburgh Healthcare SystemPittsburghUSA
        7. 7.Department of Neurobiology and NeurologyBarrow Neurological InstitutePhoenixUSA

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