P‐tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status

Campbell, Michelle R.; Ashrafzadeh-Kian, Susan; Petersen, Ronald C.; Mielke, Michelle M.; Syrjanen, Jeremy; Harten, Argonde C. van; Lowe, Val J.; Jack, Clifford R.; Bornhorst, Joshua A.; Algeciras‐Schimnich, Alicia

doi:10.1002/dad2.12190

Cited by 47 publications

(54 citation statements)

References 47 publications

(122 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The p-tau181/Aβ1-42 ratio has long been considered to have the best statistical power of the CSF markers for representing AD, as it incorporates both hallmarks of the AD disease pathway and represents a later stage of the disease pathway. Indeed this ratio in CSF has helped identify late stage changes in synaptic and neuronal degradation markers and inflammatory markers associated with AD [37], as well as show high concordance with Aβ-PET [15][16][17]20]. Here analyses of the plasma markers at a second time point in this study showed increased performance of all markers, including the p-tau181/Aβ1-42 ratio, at predicting amyloid status at Assessment 2, which may reflect further accumulation of positive biomarker signals compared to a static baseline in the amyloid negative cohort.…”

Section: Discussionmentioning

confidence: 89%

“…For example plasma Aβ1-42 and the Aβ1-42/1-40 ratio predict brain Aβ burden, and tau measured at different phosphorylation sites (threonine181 (p-tau181), threonine217 (p-tau217), threonine231 (p-tau231)) shows concordance with CSF p-tau levels (concordance ~0.8) and can predict Aβ-PET burden (AUC values ranging from 0.8 through 0.9) [9][10][11][12][13][14]. Clinical-pathological models show that understanding about the presence and severity of AD is improved when markers of amyloid and tau levels are considered simultaneously [15][16][17][18], however, to date, only one small study has investigated how combinations of plasma levels of Aβ and p-tau relate to Aβ-PET burden [19]. The first aim of this study was to investigate whether two different plasma p-tau markers (p-tau181 and p-tau231), incorporated into a ratio with Aβ, can improve predictions of Aβ burden over single analytes in comparison to PET or CSF sampling.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Fowler

Stoops²,

Rainey‐Smith

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: In Alzheimer′s disease, plasma Aβ1–42 and p–tau predict high amyloid status from Aβ–PET, however the extent to which combination of both plasma assays predict remains unknown. Methods: Prototype Simoa assays were used to measure plasma samples from cognitively normal (CN) and symptomatic adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Results: The p–tau181/Aβ1–42 ratio showed the best prediction of Aβ–PET across all participants (AUC=0.905, 95%CI:0.86–0.95) and in CN (AUC=0.873; 0.80–0.94), and symptomatic (AUC=0.908; 0.82–1.00) adults. Plasma p–tau181/Aβ1–42 ratio correlated with CSF–p–tau181 (Elecsys®, Spearman′s ρ=0.74, P<0.0001) and predicted abnormal CSF Aβ (AUC=0.816, 0.74–0.89). The p-tau181/Aβ1–42 ratio also predicted future rates of cognitive decline assessed by AIBL PACC or CDR–SOB (P<0.0001). Discussion: Plasma p–tau181/Aβ1–42 ratio predicted both Aβ–PET status and cognitive decline, demonstrating potential as both a diagnostic aid and as a screening and prognostic assay for preclinical Alzheimer′s disease trials.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Fowler

Stoops²,

Rainey‐Smith

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Current results of the association of the EV concentration/size ratio with the p-Tau 181/Aβ 42 ratio, as CSF biomarkers of AD [42], are in this direction. The EV concentration/size ratio with the p-Tau 181/Aβ 42 ratio correlation was found for the entire PTS group but the stratified analysis for dementia diagnostic categories revealed that this effect was driven by the AD group.…”

Section: Discussionmentioning

confidence: 98%

Cerebrospinal Fluid EV Concentration and Size Are Altered in Alzheimer’s Disease and Dementia with Lewy Bodies

Longobardi

Nicsanu

Bellini

et al. 2022

Cells

View full text Add to dashboard Cite

Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) represent the three major neurodegenerative dementias characterized by abnormal brain protein accumulation. In this study, we investigated extracellular vesicles (EVs) and neurotrophic factors in the cerebrospinal fluid (CSF) of 120 subjects: 36 with AD, 30 with DLB, 34 with FTD and 20 controls. Specifically, CSF EVs were analyzed by Nanoparticle Tracking Analysis and neurotrophic factors were measured with ELISA. We found higher EV concentration and lower EV size in AD and DLB groups compared to the controls. Classification tree analysis demonstrated EV size as the best parameter able to discriminate the patients from the controls (96.7% vs. 3.3%, respectively). The diagnostic performance of the EV concentration/size ratio resulted in a fair discrimination level with an area under the curve of 0.74. Moreover, the EV concentration/size ratio was associated with the p-Tau181/Aβ42 ratio in AD patients. In addition, we described altered levels of cystatin C and progranulin in the DLB and AD groups. We did not find any correlation between neurotrophic factors and EV parameters. In conclusion, the results of this study suggest a common involvement of the endosomal pathway in neurodegenerative dementias, giving important insight into the molecular mechanisms underlying these pathologies.

show abstract

“… 27 Second, the cognitive decline associated with two AD proteinopathies, using the ratio of tau pathology to Aβ, was exaggerated in those with severe asthma, in line with previous reports that the ratio of these two biomarkers was more sensitive and specific in terms of amyloid PET agreement than the individual biomarkers. 51 , 52 The association of severe asthma with elevated α‐synuclein is less specific to AD. Even though α‐synuclein is considered useful for the differential diagnosis of AD when combined with other biomarkers 53 and may contribute to AD pathophysiology, it is also present in other forms of dementia.…”

Section: Discussionmentioning

confidence: 99%

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Nair

Hulle

Bendlin

et al. 2022

A&D Transl Res & Clin Interv

View full text Add to dashboard Cite

Introduction Evidence from epidemiology, neuroimaging, and animal models indicates that asthma adversely affects the brain, but the nature and extent of neuropathophysiological impact remain unclear. Methods We tested the hypothesis that asthma is a risk factor for dementia by comparing cognitive performance and cerebrospinal fluid biomarkers of glial activation/neuroinflammation, neurodegeneration, and Alzheimer's disease (AD) pathology in 60 participants with asthma to 315 non‐asthma age‐matched control participants (45–93 years), in a sample enriched for AD risk. Results Participants with severe asthma had higher neurogranin concentrations compared to controls and those with mild asthma. Positive relationships between cardiovascular risk and concentrations of neurogranin and α‐synuclein were amplified in severe asthma. Severe asthma also amplified the deleterious associations that apolipoprotein E ε4 carrier status, cardiovascular risk, and phosphorylated tau 181 /amyloid beta 42 have with rate of cognitive decline. Discussion Our data suggest that severe asthma is associated with synaptic degeneration and may compound risk for dementia posed by cardiovascular disease and genetic predisposition. Highlights Those with severe asthma showed evidence of higher dementia risk than controls evidenced by: higher levels of the synaptic degeneration biomarker neurogranin regardless of cognitive status, cardiovascular or genetic risk, and controlling for demographics. steeper increase in levels of synaptic degeneration biomarkers neurogranin and α‐synuclein with increasing cardiovascular risk. accelerated cognitive decline with higher cardiovascular risk, genetic predisposition, or pathological tau.

show abstract

P‐tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status

Cited by 47 publications

References 47 publications

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Cerebrospinal Fluid EV Concentration and Size Are Altered in Alzheimer’s Disease and Dementia with Lewy Bodies

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Contact Info

Product

Resources

About

P‐tau/Aβ42 and Aβ42/40 ratios in CSF are equally predictive of amyloid PET status

Cited by 47 publications

References 47 publications

Plasma p-tau181/Aβ1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42and future cognitive decline

Plasma p-tau181/Aβ1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ1-42and future cognitive decline

Cerebrospinal Fluid EV Concentration and Size Are Altered in Alzheimer’s Disease and Dementia with Lewy Bodies

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Contact Info

Product

Resources

About

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline

Plasma p-tau181/Aβ_1-42ratio predicts Aβ-PET status and correlates with CSF-p-tau181/Aβ_1-42and future cognitive decline