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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Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease
Faraz Ahmad,Kunal Pratap Singh,Debajyoti Das,Ruturaj Gowaikar,Eisha Shaw,Arathy Ramachandran,Khader Valli Rupanagudi,Reddy Peera Kommaddi,David A. Bennett,Vijayalakshmi Ravindranath +9 more
TL;DR: It is demonstrated that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance.
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Structure-Function Relationships behind the Phenomenon of Cognitive Resilience in Neurology: Insights for Neuroscience and Medicine
TL;DR: The study of resilience will illuminate ways by which the brain can overcome adversity and help inform prevention and treatment strategies and is relevant to combating the negative neuropsychological impact of aging and fostering cognitive enhancement.
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Subtypes based on cerebrospinal fluid and magnetic resonance imaging markers in normal elderly predict cognitive decline
Jasmine Nettiksimmons,Danielle J Harvey,Jerry D. Brewer,Owen Carmichael,Charles DeCarli,Clifford R. Jack,R. C. Petersen,Leslie M. Shaw,John Q. Trojanowski,Michael W. Weiner,Laurel A. Beckett +10 more
TL;DR: Individual biomarkers had limited predictive value for cognitive decline, but membership in the cluster with the most extreme profile was associated with more rapid decline in ADAS-cog and subtypes among NC based on multiple biomarkers may represent the earliest stages of subclinical cognitive decline and AD.
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Biomarkers of Alzheimer's disease and mild cognitive impairment: A current perspective
TL;DR: The NDD tools enable the diagnosis of AD already in the early preclinical stage, as the first pathophysiologic events observable in the CSF and amyloid β-PET occur years and perhaps decades before the onset of the earliest clinical symptoms.
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Early Cognitively Based Functional Limitations Predict Loss of Independence in Instrumental Activities of Daily Living in Older Adults
TL;DR: It is indicated that early functional limitations have prognostic value in identifying older adults at risk for developing functional disability and the importance of developing interventions to support everyday abilities related to memory, executive function, and visuospatial skills in an effort to delay loss of independence in IADLs.
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