Cerebrospinal Fluid Markers of Neurodegeneration and Rates of Brain Atrophy in Early Alzheimer Disease

Tarawneh, Rawan; Head, Denise; Allison, Samantha L.; Buckles, Virginia; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.

doi:10.1001/jamaneurol.2015.0202

Cited by 79 publications

(83 citation statements)

References 73 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2A). This average number range was slightly lower than CSF tau measured from live human subjects (26). CSF tau linearly correlates with Braak stage (Spearman r ¼ 0.4153, p ¼ 0.03, Fig.…”

Section: Total Tau Protein In Csf Was Not Driven By Soluble Brain Taumentioning

confidence: 71%

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Han

Serrano

Beach

et al. 2017

J Neuropathol Exp Neurol

View full text Add to dashboard Cite

Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.

show abstract

“…2A). This average number range was slightly lower than CSF tau measured from live human subjects (26). CSF tau linearly correlates with Braak stage (Spearman r ¼ 0.4153, p ¼ 0.03, Fig.…”

Section: Total Tau Protein In Csf Was Not Driven By Soluble Brain Taumentioning

confidence: 71%

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Han

Serrano

Beach

et al. 2017

J Neuropathol Exp Neurol

View full text Add to dashboard Cite

show abstract

“…Neurogranin is a calmodulin-binding postsynaptic 15 neuronal protein 16 that is abundantly expressed in perikaryal and dendritic cytoplasm 15 Neurogranin is thought to be involved in activity-dependent synaptic plasticity and long-term potentiation through the modulation of calcium-mediated signaling pathways 17 – 19 Because of its abundant and preferential neuronal expression, neurogranin has been identified as a potential marker of neurodegeneration in large-scale gene arrays, 20 along with other candidate markers, such as visinin-like protein-1 (VILIP-1) 21–23 Previous studies suggest that cerebrospinal fluid (CSF) neurogranin levels are elevated in AD 24 and predict conversion from mild cognitive impairment (MCI) to AD dementia 25–27 …”

mentioning

confidence: 99%

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease

et al. 2016

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD.OBJECTIVE To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F.

show abstract

“…In AD, tau specificity (65-86%) and sensitivity (40-86%) levels have been determined and, although the ranges are highly dependent on the cohorts analysed and the age of the patients, a cut-off value of 450 pg/ml is commonly used for diagnostic purposes (Humpel, 2011). Tau levels also correlate with regional brain atrophy in early AD, showing a potential predictive value (Tarawneh et al, 2015). It is worth mention that total tau does not remain elevated in stroke in contrast to CJD which remains increased in follow up examination.…”

Section: Tau P-tau and Ab Peptidesmentioning

confidence: 99%