Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study

Hanon, Olivier; Vidal, Jean‐Sébastien; Lehmann, Sylvain; Bombois, Stéphanie; Allinquant, Bernadette; Baret-Rose, Christiane; Tréluyer, Jean‐Marc; Abdoul, Hendy; Gelé, Patrick; Delmaire, Christine; Blanc‬, ‪Frederic; Mangin, Jean‐François; Buée, Luc; Touchon, Jacques; Hugon, Jacques; Vellas, Bruno; Galbrun, Evelyne; Bénétos, Athanase; Berrut, Gilles; Paillaud, Éléna; Wallon, David; Castelnovo, Giovanni; Volpe‐Gillot, Lisette; Pocard, Marc; Robert, Philippe; Godefroy, Olivier; Camus, Vincent; Belmin, Joël; Vandel, Pierre; Novella, Jean‐Luc; Duron, Emmanuelle; Rigaud, Anne‐Sophie; Schraen‐Maschke, Susanna; Gabelle, Audrey

doi:10.1002/alz.12613

Cited by 23 publications

(36 citation statements)

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“…As already reported in BALTAZAR 6 and illustrated in Table 1, at baseline, the MCI converters to dementia were older, had a lower MMSE score, were more often APOE ε4 carriers and had more severe hippocampal atrophy. CSF Aβ1-40, Aβ1-42, Tau and p-Tau181 values available in a part of the MCI population (n= 214; as lumbar puncture was optional) were also highly differential between MCI that converted or not.…”

Section: Comparison Between MCI Converters and Non-converterssupporting

confidence: 73%

“…Patient underwent visits every six months for three years. MCI participants were reassessed for conversion to dementia at each visit by the clinician 6 . The progression from MCI to dementia was defined by evaluation of the following parameters: decline in cognitive functioning (measured by changes from the baseline in scores of the mini mental state examination [MMSE]), and disability in activities of daily living (instrumental activities of daily living iADL>1 and clinical dementia rating sum of boxes ( > 1).…”

Section: Methodsmentioning

confidence: 99%

“…CSF Aβ1-40, Aβ1-42, Tau and p-Tau181 values available in a part of the MCI population (n= 214; as lumbar puncture was optional) were also highly differential between MCI that converted or not. We have previously described that plasma amyloid biomarkers measured with an early generation of assay in the BALTAZAR cohort 6 showed differential level. More interestingly, plasma P-tau181 increased significantly on average by 30% between MC non-converters at 2•9 [SD 1•4] pg/mL and converters at 3•8 [SD 1•5] pg/mL (p<0•0001).…”

Section: Comparison Between MCI Converters and Non-convertersmentioning

confidence: 99%

“…Their relevance has already been proven in cerebrospinal fluid (CSF) justifying their implementation in clinical routine 4,5 . Thanks to ultrasensitive assays and mass spectrometry approaches, blood amyloid peptides were the first to show a significant detection of amyloid positive (Aβ+) patients as defined by amyloid PET or CSF analysis or to predict evolution of patients within the AD continuum, including conversion of patients with a mild cognitive impairment (MCI) to dementia 6 . While the detection of total tau in blood was not so discriminating 7 , the ability to detect its phosphorylated forms at position threonine 181 (P-tau181) was a real breakthrough 8 .…”

Section: Introductionmentioning

confidence: 99%

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Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Lehmann

Schraen‐Maschke

Vidal

et al. 2022

Preprint

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BackgroundPlasma P-tau181 is associated with tau and amyloid pathology in Alzheimer’s disease (AD). Its use as a biomarker for the detection of AD (along the disease continuum, from preclinical to mild cognitive impairment (MCI) and dementia) is increasingly established, as is its prognostic value. Further validation in different settings of use is still needed, as well as investigation of confounding factors that might indirectly influence its blood concentration.MethodsThis study is ancillary to the prospective multicenter BALTAZAR cohort that enrolled patients with MCI according to Petersen criteria. Amyloid-positive (Aβ+) status was based on assessment of the cerebrospinal fluid (CSF) Aβ1-42/Aβ1-40 ratio, and participants were examined for conversion to dementia for up to three years. Plasma Ptau-181 was measured using an ultrasensitive assay and its diagnostic performance for Aβ+ and conversion to dementia were studied, as well as evaluation of the impact of comorbidities and biological confounders.FindingsAmong 476 MCI participants (mean MMSE score of 26·4 [SD 2·5] and 39·8% carrying APOE ε4), 67% were Aβ+ and 30% developed dementia (95% probable AD) at a mean of 14·6 [SD 8·2] months after the baseline. Independently of age, sex, and APOEε4, plasma P-tau181 was increased significantly by 30% between non-converters and converters (2·9 [SD 1·4] vs. 3·8 [SD 1·5] pg/mL, p<0·0001) and by 50% between Aβ- and Aβ+ (2·6 [SD 1·4] vs. 3·9 [SD 1·4] pg/mL, p<0·0001). Logistic regression was used to compare conversion and Aβ+ detection combining age, sex, APOEε4 status and MMSE without or with the addition of plasma P-tau181 which significantly improves performance (AUC 0·691 to 0·744 for conversion and 0·786 to 0·849 for Aβ+). CSF P-tau181 did not perform better in the same setting. Using a linear regression approach, chronic kidney disease (CKD), creatinine and glomerular filtration rate were independently associated with plasma P-tau181 concentrations, thereby altering the optimal cutpoints for Aβ+ or conversion to dementia detection.InterpretationPlasma P-tau181 effectively detects Aβ+ and conversion to dementia in a manner similar to CSF P-tau181, making this blood biomarker central to AD management. However, renal function significantly alters concentrations and will induce diagnostic error if not systematically taken into account.

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Section: Comparison Between MCI Converters and Non-converterssupporting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Comparison Between MCI Converters and Non-convertersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Lehmann

Schraen‐Maschke

Vidal

et al. 2022

Preprint

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“…Administration of coenzyme Q10 could attenuate amyloid β accumulation and mitigate Alzheimer’s-like behavioral and pathological symptoms ( Yang et al, 2008 ; Muthukumaran et al, 2018 ; Ibrahim Fouad, 2020 ). Recent published data showed that lower levels of amyloid β-42 and amyloid β-42/40 ratio was found in dementia patients ( Hanon et al, 2022 ; Thijssen et al, 2022 ), but other researchers found that patients with dementia had higher levels of amyloid β-42, and the level of plasma amyloid β-42/40 ratio was correlated with amyloid positivity in the bilateral frontal, parietal, temporal, and occipital cortices ( Manafikhi et al, 2021 ; Yun et al, 2021 ). The levels of amyloid β-42 and β-40 in dementia patients appear to remain uncertain.…”

Section: Discussionmentioning

confidence: 99%

Investigation of coenzyme Q10 status, serum amyloid-β, and tau protein in patients with dementia

Chang

Chou²,

Lai³

et al. 2022

Front. Aging Neurosci.

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ObjectivesDementia is an oxidative stress-related disease. Coenzyme Q10 is a nutrient that occurs naturally in the human body and acts as an antioxidant. The purpose of this study was to investigate the relationships of coenzyme Q10 status, biomarkers for dementia (amyloid β and tau protein), and antioxidant capacity in patients with dementia.MethodsEighty dementia patients aged ≥60 years and with a mini mental state examination (MMSE) score ≤ 26 were enrolled. The levels of coenzyme Q10, total antioxidant capacity (TAC), amyloid β, and tau protein were measured.ResultsA total of 73% of patients had a low coenzyme Q10 status. Patients with low coenzyme Q10 status had a significantly higher level of serum amyloid β-42 and amyloid β-42/40 ratio (p < 0.05). Coenzyme Q10 status was significantly correlated with the values of TAC, MMSE score, amyloid β-42, and amyloid β-42/40 ratio (p < 0.05) but not with tau protein. Additionally, a high proportion of moderate dementia patients were found to have low coenzyme Q10 status (p = 0.07).ConclusionPatients with dementia suffered from coenzyme Q10 deficiency, and the degree of deficiency was related to the level of amyloid-β and antioxidant capacity. Since adequate level of coenzyme Q10 may delay the progression of dementia, monitoring coenzyme Q10 status in patients with dementia is necessary.

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Annual stability of the plasma Aß40/42 ratio and associated factors

Nakamura

Kawarabayashi

Nakahata

et al. 2023

Ann Clin Transl Neurol

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Objective: The plasma Aß40/42 ratio is a biomarker of brain amyloidosis. However, the threshold difference between amyloid positivity and negativity is only 10-20% and fluctuates with circadian rhythms, aging, and APOE-e4 during the decades of evolution of Alzheimer's disease. Methods: Plasma Aß40 and Aß42 levels in 1472 participants aged between 19 and 93 years in the Iwaki Health Promotion Project for 4 years were statistically analyzed. Results: The means and standard deviations of annual inter-individual coefficients of variation were 5.3 AE 3.2% for Aß40, 7.8 AE 4.6% for Aß42, and 6.4 AE 4.1% for the Aß40/42 ratio. No significant age-dependent changes were observed in interindividual coefficients of variation. Age-dependent increases in Ab42 levels were suppressed, whereas those in the Ab40/42 ratio were enhanced in APOE-e4 carriers. The change points of Aß42, Aß40, and the Aß40/42 ratio were 36.4, 38.2, and 43.5 years, respectively. In the presence of APOE-e4, the Aß40/42 ratio increased in middle-aged and elderly subjects while Ab42 levels decreased in elderly subjects. Interpretation: Individual values for Aß40, Aß42, and the Aß40/42 ratio did not fluctuate annually or in an age-dependent manner. If the plasma Ab40/42 ratio changes by more than 14.7% (+2 standard deviations) relative to age-and APOE-e4-adjusted normal annual fluctuations, other biomarkers also need to be examined.

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Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study

Cited by 23 publications

References 50 publications

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Investigation of coenzyme Q10 status, serum amyloid-β, and tau protein in patients with dementia

Annual stability of the plasma Aß40/42 ratio and associated factors

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