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PMID: 20083042 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Lancet. Neurology ·Vol. 9 ·No. 1 ·2010-01-00 ·Pages 119-28

Jack CR, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ

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.

MeSH Terms
Aging/genetics,pathology,physiology Alzheimer Disease/genetics,pathology,physiopathology Amyloid beta-Peptides/cerebrospinal fluid,metabolism Apolipoprotein E4/genetics Biomarkers/cerebrospinal fluid,metabolism Brain/diagnostic imaging,pathology,physiopathology Cognition Disorders/genetics,pathology,physiopathology Disease Progression Humans Magnetic Resonance Imaging Models, Neurological Plaque, Amyloid/genetics,metabolism,pathology Positron-Emission Tomography Signal Transduction Time Factors tau Proteins/cerebrospinal fluid,metabolism
Chemicals
Amyloid beta-Peptides Apolipoprotein E4 Biomarkers MAPT protein, human tau Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Jack Clifford R
Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA. jack.cliff [email protected]
Knopman David S
Jagust William J
Shaw Leslie M
Aisen Paul S
Weiner Michael W
Petersen Ronald C
Trojanowski John Q
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Article Info
Journal
The Lancet. Neurology
Abbr.
Lancet Neurol
ISSN
1474-4465
DOI
10.1016/S1474-4422(09)70299-6
Email
[email protected]
Published
2010-01-00
Pages
119-28
Language
English
Region
England
NLM ID
101139309
PMCID
PMC2819840
Subset
IM
Grants
NIA NIH HHS · P30 AG010124 · United States
NIA NIH HHS · AG06786 · United States
NIA NIH HHS · P30 AG010124-18 · United States
NIA NIH HHS · AG10124 · United States
NIA NIH HHS · P50 AG016574 · United States
NIA NIH HHS · U19 AG010483 · United States
NIA NIH HHS · R01 AG011378 · United States
NIA NIH HHS · U01 AG006786-24 · United States
NIA NIH HHS · P50 AG016574-11 · United States
NIA NIH HHS · AG11378 · United States
NIA NIH HHS · R01 AG011378-17 · United States
NIA NIH HHS · AG16574 · United States
NIA NIH HHS · U01 AG006786 · United States
External Links
PubMed source DOI: 10.1016/S1474-4422(09)70299-6 PMC Full Text View journal details
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