Tau Kinetics in Neurons and the Human Central Nervous System

Sato, Chihiro; Barthélemy, Nicolas R.; Mawuenyega, Kwasi G.; Patterson, Bruce W.; Gordon, Brian A.; Jockel-Balsarotti, Jennifer; Sullivan, Melissa; Crisp, Matthew J.; Kasten, Tom; Kirmess, Kristopher M.; Kanaan, Nicholas M.; Yarasheski, Kevin E.; Baker-Nigh, Alaina; Benzinger, Tammie L.S.; Miller, Timothy M.; Karch, Celeste M.; Bateman, Randall J.

doi:10.1016/j.neuron.2018.02.015

Cited by 444 publications

(496 citation statements)

References 80 publications

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“…We found that independent of Aβ1‐42, levels of synaptic biomarkers expressed as ratios relative to Tau, in particular, NPTX2/Tau, achieved high classification accuracy. NPTX2 is decreased in the brain and CSF in AD, reflecting the loss of a key mechanism of synaptic homeostasis, whereas CSF Tau is increased, reflecting AD‐related damage to neurons that may lead to regulated increases in the secretion of proteolytically cleaved Tau [34]. The ratio combining measures of these two processes seems to capture neurodegeneration in a way that correlates well with impaired cognitive performance, and can, therefore, track early stages of cognitive decline in AD.…”

Section: Discussionmentioning

confidence: 99%

Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease

Galasko

Xiao

et al. 2019

A&D Transl Res & Clin Interv

100

129

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Introduction Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Results There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aβ1‐42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aβ1‐42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2–3‐year decline. We replicated findings in the ADNI cohort. Discussion CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1‐42 and Tau. This is relevant for prognosis and clinical trials.

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Section: Discussionmentioning

confidence: 99%

Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease

Galasko

Xiao

et al. 2019

A&D Transl Res & Clin Interv

100

129

View full text Add to dashboard Cite

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“…Tau tangles block the transport of nutrients and other essential molecules inside neurons. Although the complete sequence of events is unclear, beta‐amyloid may begin accumulating before abnormal tau, and increasing beta‐amyloid accumulation is associated with subsequent increases in tau 7,8 …”

Section: Overview Of Alzheimer's Diseasementioning

confidence: 99%

“…Although the complete sequence of events is unclear, beta-amyloid may begin accumulating before abnormal tau, and increasing beta-amyloid accumulation is associated with subsequent increases in tau. 7,8 Other brain changes include inflammation and atrophy. The presence of toxic beta-amyloid and tau proteins are believed to activate immune system cells in the brain called microglia.…”

Section: Brain Changes Associated With Alzheimer's Diseasementioning

confidence: 99%

2020 Alzheimer's disease facts and figures

2020

Alzheimer's & Dementia

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This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society. The Special Report discusses the future challenges of meeting care demands for the growing number of people living with Alzheimer's dementia in the United States with a particular emphasis on primary care. By mid‐century, the number of Americans age 65 and older with Alzheimer's dementia may grow to 13.8 million. This represents a steep increase from the estimated 5.8 million Americans age 65 and older who have Alzheimer's dementia today. Official death certificates recorded 122,019 deaths from AD in 2018, the latest year for which data are available, making Alzheimer's the sixth leading cause of death in the United States and the fifth leading cause of death among Americans age 65 and older. Between 2000 and 2018, deaths resulting from stroke, HIV and heart disease decreased, whereas reported deaths from Alzheimer's increased 146.2%. In 2019, more than 16 million family members and other unpaid caregivers provided an estimated 18.6 billion hours of care to people with Alzheimer's or other dementias. This care is valued at nearly $244 billion, but its costs extend to family caregivers’ increased risk for emotional distress and negative mental and physical health outcomes. Average per‐person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are more than three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 23 times as great. Total payments in 2020 for health care, long‐term care and hospice services for people age 65 and older with dementia are estimated to be $305 billion. As the population of Americans living with Alzheimer's dementia increases, the burden of caring for that population also increases. These challenges are exacerbated by a shortage of dementia care specialists, which places an increasing burden on primary care physicians (PCPs) to provide care for people living with dementia. Many PCPs feel underprepared and inadequately trained to handle dementia care responsibilities effectively. This report includes recommendations for maximizing quality care in the face of the shortage of specialists and training challenges in primary care.

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“…Various mechanisms have been described by which tau aggregates can be released or taken up by cells . However, it has recently become clear that tau is released by neurons in both health and disease . This suggests that tau, apart from interacting with microtubules, has other functions as well .…”

Section: Psp: Milestones Of the Recent 10 Yearsmentioning

confidence: 99%

One decade ago, one decade ahead in progressive supranuclear palsy

2019

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Fifty‐five years have passed from the first description of PSP, but it is in the last decade that there has been a revolutionary change in understanding both clinical and pathophysiological aspects of this disease. Ten years ago, our knowledge about the clinical spectrum and pathophysiology of the disease was quite limited, and there was no credible clinical study on any drug treatment for this devastating disease. Today, we have discovered the wide clinical spectrum of PSP, and this led to the development of new diagnostic criteria in 2017, aiming to diagnose the disease earlier and include more phenotypes into clinical studies. Moreover, just over the past 10 years, numerous large, double‐blind, clinical trials with disease‐modifying agents have been conducted that provided important novel insights into disease biomarkers and progression. These studies were possible because of gained novel insights into pathophysiological processes of the disease and pave the way for the near future. In the next decade, we dare to predict the discovery of biomarkers for PSP, improvements in diagnosis using the new criteria in combination with these biomarkers, and ultimately the development of a neuroprotective therapy that could be applied to patients in a prodromal stage and spare them from this devastating disorder. © 2019 International Parkinson and Movement Disorder Society

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Tau Kinetics in Neurons and the Human Central Nervous System

Cited by 444 publications

References 80 publications

Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease

Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease

2020 Alzheimer's disease facts and figures

One decade ago, one decade ahead in progressive supranuclear palsy

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