Hypothetical Model of Dynamic Biomarkers of the Alzheimer's Pathological Cascade

Overview

Journal Lancet Neurol

Specialty Neurology

Date 2010 Jan 20

PMID 20083042

Citations 2116

Authors

Clifford R Jack Jr

David S Knopman

William J Jagust

Leslie M Shaw

Paul S Aisen

Michael W Weiner

Ronald C Petersen

John Q Trojanowski

Affiliations

Soon will be listed here.

Abstract

Currently available evidence strongly supports the position that the initiating event in Alzheimer's disease (AD) is related to abnormal processing of beta-amyloid (Abeta) peptide, ultimately leading to formation of Abeta plaques in the brain. This process occurs while individuals are still cognitively normal. Biomarkers of brain beta-amyloidosis are reductions in CSF Abeta(42) 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 Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.

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