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

Han, Pengcheng; Serrano, Geidy E.; Beach, Thomas G.; Caselli, Richard J.; Yin, Jun; Zhuang, Ningning; Shi, Jiong

doi:10.1093/jnen/nlw105

Cited by 27 publications

(45 citation statements)

References 33 publications

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“…Among other clinical criteria 33 , CSF biomarkers are required in the determination of MCI due to AD, such as CSF Aβ 1-42 , total-Tau, and/or p-Tau concentrations 32 . Several studies in the literature have shown a significant difference in CSF Aβ 1-42 [34][35][36] , total-Tau [35][36][37][38][39] , and p-Tau 37 concentrations between MCI and AD patients, describing a decrease in the CSF Aβ 1-42 concentration ([Aβ 1-42 ] CSF ) and an increase in the CSF total-Tau and p-Tau concentrations ([Tau] CSF and [p-Tau] CSF ) in AD patients. However, these differences are not always statistically significant for CSF Aβ 1-42 37,40 , total-Tau 34,40 , and p-Tau 34,35,39,40 .…”

Section: Early Stage Of Ad: Csf and Plasma Biomarkersmentioning

confidence: 99%

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

et al. 2020

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Recent evidence showing degeneration of the noradrenergic system in the locus coeruleus (LC) in Alzheimer's disease (AD) has motivated great interest in noradrenaline (NA) as a potential brain hallmark of the disease. Despite the current exploration of blood markers for AD, the deregulation of the plasma NA concentration ([NA] plasma) in AD is currently not well understood. This retrospective study includes a cohort of 71 patients (32 AD patients, 22 with other dementia and 17 without dementia) who were given consultations for memory complaints in the Cognitive Neurology Center of Lariboisière (Paris) between 2009 and 2014. As previously described in brain tissue, we show for the first time a linear correlation between [NA] plasma and Mini Mental State Examination (MMSE) score in AD patients. We observed that high [NA] plasma in AD patients was associated with higher [Aβ 1-42 ] CSF than in other AD patients with [NA] plasma similar to NC patients. In parallel, we observed a lower (p-Tau/Tau) CSF in AD patients with low [NA] plasma than in non-AD patients with [NA] plasma similar to [NA] plasma in NC patients. Our data suggest that [NA] plasma could be a potential biomarker of disease evolution in the context of AD and could possibly improve early diagnosis.

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Section: Early Stage Of Ad: Csf and Plasma Biomarkersmentioning

confidence: 99%

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

et al. 2020

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“…This was particularly evident in the proteomics data, where levels of sarkosyl-insoluble total tau were not different between APP swe / PS1 ΔE9 and control mice, but were > 30-fold elevated in AD vs. non-AD subjects. Studies estimating 65 and measuring 66 the amount of insoluble tau protein in the human AD brain show that tau levels are significantly higher than control in symptomatic AD patients, but not in patients with prodromal or preclinical AD. It might thus be that the tau pathology we detect in APP swe / PS1 ΔE9 mice corresponds to early stage AD.…”

Section: Discussionmentioning

confidence: 98%

Ageing and amyloidosis underlie the molecular and pathological alterations of tau in a mouse model of familial Alzheimer’s disease

Metaxas

Thygesen

Kempf

et al. 2019

Sci Rep

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Despite compelling evidence that the accumulation of amyloid-beta (Aβ) promotes neocortical MAPT (tau) aggregation in familial and idiopathic Alzheimer’s disease (AD), murine models of cerebral amyloidosis are not considered to develop tau-associated pathology. In the present study, we show that tau can accumulate spontaneously in aged transgenic APPswe/PS1ΔE9 mice. Tau pathology is abundant around Aβ deposits, and further characterized by accumulation of Gallyas and thioflavin-S-positive inclusions, which were detected in the APPswe/PS1ΔE9 brain at 18 months of age. Age-dependent increases in argyrophilia correlated positively with binding levels of the paired helical filament (PHF) tracer [18F]Flortaucipir, in all brain areas examined. Sarkosyl-insoluble PHFs were visualized by electron microscopy. Quantitative proteomics identified sequences of hyperphosphorylated and three-repeat tau in transgenic mice, along with signs of RNA missplicing, ribosomal dysregulation and disturbed energy metabolism. Tissue from the frontal gyrus of human subjects was used to validate these findings, revealing primarily quantitative differences between the tau pathology observed in AD patient vs. transgenic mouse tissue. As physiological levels of endogenous, ‘wild-type’ tau aggregate secondarily to Aβ in APPswe/PS1ΔE9 mice, this study suggests that amyloidosis is both necessary and sufficient to drive tauopathy in experimental models of familial AD.

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“…In contrast to Aβ, the vast majority of tau protein can be isolated within aqueous or detergent soluble fractions. In non-AD cases, as much as 97% of tau can be recovered from the soluble fraction, whilst in AD this is considerable lower (~50%) due to the accumulation of insoluble aggregates (Mukaetova-Ladinska et al, 1993;Tremblay et al, 2007;Han et al, 2017). Insoluble tau isolated from human AD brains is 3-4-fold higher compared to non-AD brains (Hanger et al, 1991;Ksiezak-Reding et al, 1992) and levels within temporal and parietal regions are robustly elevated mirroring the regional burden of NFTs.…”

Section: Introductionmentioning

confidence: 99%

Distinctive temporal profiles of detergent-soluble and -insoluble tau and Aβ species in human Alzheimer’s disease

et al. 2018

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Alzheimer's disease (AD) pathology relevant proteins tau and beta-amyloid (Aβ) exist as an array of post-translationally modified and conformationally altered species with varying abundance, solubility and toxicity. Insoluble neurofibrillary tau tangles and Aβ plaques are end-stage AD hallmarks, yet may carry less disease significance compared to soluble species. At present, it is unclear how soluble and insoluble tau and Aβ relate to each other as well as to disease progression. Here, detergent soluble and insoluble fractions generated from post-mortem human temporal lobe samples (Brodmann area 21) were probed for tau and Aβ markers in immuno-dot assays. Measures were quantified according to diagnosis (AD cf. Non-AD), neuropathological severity, and correlated with disease progression (Braak stages). All markers were elevated within AD cases cf. non-AD controls (p < 0.05) independent of solubility. However, when considered according to neuropathological severity, phospho-tau (detected via CP13 and AT8 antibodies) was elevated early within the soluble fraction (p < 0.05 intermediate cf. low severity) and emerged only later within the insoluble fraction (p < 0.05 high cf. low severity). In contrast, PHF1 phospho-tau, TOC1 reactive tau oligomers and amyloid markers rose within the two fractions simultaneously. Independent of solubility, cognitive correlations were observed for tau makers and for fibrillary amyloid (OC), however only soluble total Aβ was significantly correlated with intellectual impairment. Following the exclusion of end-stage cases, only soluble total Aβ remained correlated with cognition. The data indicate differential rates of protein aggregation during AD progression and confirm the disease relevance of early emerging soluble Aβ species.

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

Cited by 27 publications

References 33 publications

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

Correlation between cognition and plasma noradrenaline level in Alzheimer’s disease: a potential new blood marker of disease evolution

Ageing and amyloidosis underlie the molecular and pathological alterations of tau in a mouse model of familial Alzheimer’s disease

Distinctive temporal profiles of detergent-soluble and -insoluble tau and Aβ species in human Alzheimer’s disease

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