Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade

Clifford R. Jack, David S. Knopman, William J. Jagust, Leslie M. Shaw, Paul S. Aisen, Michael W. Weiner, Ronald C. Petersen, John Q. Trojanowski

Research output: Contribution to journalComment/debate

2438 Scopus citations

Abstract

Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of β-amyloid (Aβ) peptide, ultimately leading to formation of Aβ plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain β-amyloidosis are reductions in CSF Aβ42 and increased amyloid PET tracer retention. After a lag period, which varies from patient to patient, neuronal dysfunction and neurodegeneration become the dominant pathological processes. Biomarkers of neuronal injury and neurodegeneration are increased CSF tau and structural MRI measures of cerebral atrophy. Neurodegeneration is accompanied by synaptic dysfunction, which is indicated by decreased fluorodeoxyglucose uptake on PET. We propose a model that relates disease stage to AD biomarkers in which Aβ biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalThe Lancet Neurology
Volume9
Issue number1
DOIs
StatePublished - Jan 2010

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ASJC Scopus subject areas

  • Clinical Neurology

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