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

被引：3706

作者：

Jack, Clifford R., Jr. ^{[1
]}

Knopman, David S. ^{[2
]}

Jagust, William J. ^{[3
]}

Shaw, Leslie M. ^{[4
,5
]}

Aisen, Paul S. ^{[6
]}

Weiner, Michael W. ^{[7
]}

Petersen, Ronald C. ^{[2
]}

Trojanowski, John Q. ^{[4
,5
]}

机构：

[1] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

[3] Univ Calif Berkeley, Sch Publ Hlth & Helen Wills, Inst Neurosci, Berkeley, CA 94720 USA

[4] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA

[6] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[7] Univ Calif San Francisco, San Francisco, CA 94143 USA

来源：

LANCET NEUROLOGY | 2010年 / 9卷 / 01期

基金：

美国国家卫生研究院;

关键词：

MILD COGNITIVE IMPAIRMENT; BETA-AMYLOID BURDEN; CEREBROSPINAL-FLUID A-BETA(42); GENOME-WIDE ASSOCIATION; CSF-PHOSPHORYLATED-TAU; BRAIN ATROPHY; NEUROFIBRILLARY TANGLES; APOE GENOTYPE; GENETIC RISK; FOLLOW-UP;

D O I：

10.1016/S1474-4422(09)70299-6

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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

引用

页码：119 / 128

页数：10

共 117 条

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