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 +7 more
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This work proposes a model that relates disease stage to AD biomarkers in which Abeta biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegnerative biomarker become abnormal later, and correlate with clinical symptom severity.Abstract:
Summary 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 Aβ 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 Aβ biomarkers become abnormal first, before neurodegenerative biomarkers and cognitive symptoms, and neurodegenerative biomarkers become abnormal later, and correlate with clinical symptom severity.read more
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Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology
Rebecca G. Smith,Eilis Hannon,Philip L. De Jager,Philip L. De Jager,Philip L. De Jager,Lori B. Chibnik,Lori B. Chibnik,Simon J. Lott,Daniel Condliffe,Adam Smith,Vahram Haroutunian,Vahram Haroutunian,Claire Troakes,Safa Al-Sarraj,David A. Bennett,John Powell,Simon Lovestone,Leonard C. Schalkwyk,Jonathan Mill,Katie Lunnon +19 more
TL;DR: Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain, and the role of epigenetic regulation in this dysregulation is still unclear.
Journal ArticleDOI
A sensitive aβ oligomer assay discriminates Alzheimer's and aged control cerebrospinal fluid.
Mary J. Savage,Juliya Kalinina,Abigail Wolfe,Katherine Tugusheva,Rachel Korn,Tanesha Cash-Mason,Jill W. Maxwell,Nathan G. Hatcher,Sharie J. Haugabook,Guoxin Wu,Bonnie J. Howell,John J. Renger,Paul J. Shughrue,Alexander McCampbell +13 more
TL;DR: A significant 3- to 5-fold increase in Aβ oligomers in human AD CSF compared with comparably aged controls was demonstrated, suggesting reasonable discriminatory power for the AD state and the potential for utility as a diagnostic marker.
Journal ArticleDOI
Apolipoprotein E ε4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta-analysis.
Sheila M. Crean,Alex Ward,Catherine J. Mercaldi,Jenna Collins,Michael N. Cook,Nicole L. Baker,H. Michael Arrighi +6 more
TL;DR: APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population, and study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.
Journal ArticleDOI
Ceramides as Novel Disease Biomarkers.
TL;DR: Ceramides or ceramide panel combinations have been proposed as specific disease biomarkers that could be detected in diseased tissue, synovial fluid, cerebrospinal fluid, and blood and the potential use of ceramides as biomarkers in diagnostics, determination of disease stage and personalized medicine is reviewed.
Journal ArticleDOI
Dissociating Normal Aging from Alzheimer's Disease: A View from Cognitive Neuroscience.
TL;DR: Qualitative differences in neurocognitive changes associated with normal aging and Alzheimer’s disease clearly indicate that AD cannot be simply described as accelerated aging process but on the contrary represents a solid entity.
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