Applications of Biomarkers of AD

Biomarker Changes in Autosomal Dominantly Inherited AD

Because autosomal dominantly inherited AD develops over many years, the age of onset is predictable and provides an opportunity to determine the sequence and magnitude of pathologic changes that lead to symptomatic disease. Analysis of data from a prospective, longitudinal study has revealed the following (Bateman et al. 2012):

  • • Concentrations of Ap42 in the CSF appeared to decline 25 years before expected symptom onset.
  • • Ap deposition, as measured by PET with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset.
  • • Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset.
  • • Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset.
  • • Global cognitive impairment, as measured by the MMSE and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset.
  • • Patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.

These results require confirmation with the use of longitudinal data and may not apply to patients with sporadic AD.

The findings of a study of young adults from a population in Colombia with a high prevalence of a mutation in the PSEN1 gene, which leads to the development of AD at an early age, suggests that biomarkers of AD might be apparent even earlier than thought, perhaps 20 years before the onset of symptoms (Jagust 2012). There was an increase in CSF levels of Ap in mutation carriers well in advance of clinical onset of the disease. It is hoped that early detection biomarkers could enable identification of presymptomatic AD patients and improve their therapeutic options.

 
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