Taking the A Train? Limited Consistency of Aβ42 and the Aβ42/40 Ratio in the AT(N) Classification

Gouilly, Dominique; Tisserand, Camille; Nogueira, Léonor; Saint-Lary, Laura; Rousseau, Vanessa; Benaiteau, Marie; Rafiq, Marie; Carlier, Jasmine; Milongo-Rigal, Emilie; Pagès, Jean‐Christophe; Pariente, Jérémie

doi:10.3233/jad-210236

Cited by 7 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this, a French memory clinic study reported mostly normal Aβ42/40 levels in A+T− patients and abnormal levels in A−T+ patients. 47 These results support using Aβ42/40 in clinical practice as a CSF marker of A. Aβ42/40 could be particularly informative when Aβ42 and other markers are discrepant. 46,48 Because widely accepted biomarker cutoffs do not yet exist, the normal/abnormal dichotomy in the ATN system is a challenge.…”

Section: Discussionsupporting

confidence: 67%

β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population

et al. 2022

View full text Add to dashboard Cite

Background and Objectives:ATN (β-Amyloid, Tau, Neurodegeneration) system categorizes individuals based on their core Alzheimer’s disease (AD) biomarkers. An important potential future use for ATN is therapeutic decision-making in clinical practice once disease-modifying treatments, e.g., anti-amyloid, become widely available. In this cross-sectional study, we applied ATN and estimated potential eligibility for anti-amyloid treatment in a real-life memory clinic with biomarker assessments integrated into the routine diagnostic procedure and all specialized resources available for the implementation of novel treatments.Methods:We included all consecutive patients at the Karolinska University Hospital Memory clinic in Solna, Stockholm, Sweden, who had their first diagnostic visit in April 2018–February 2021, informed consent for the clinic research database, and available clinical and biomarker (CSF, imaging) data. ATN classification was based on CSF Aβ42 (or Aβ42/40; A), CSF phosphorylated tau (T), and medial temporal lobe atrophy (N). For CSF markers, we applied laboratory cut-offs and data-driven cut-offs for comparison (determined with Gaussian mixture modelling). Anti-amyloid treatment eligibility was assessed following the published recommendations for aducanumab (AD dementia or MCI with no evidence of non-AD etiology, appropriate level of cognition, AD-consistent CSF profile).Results:Study population consisted of 410 patients (52% subjective cognitive impairment, 23% mild cognitive impairment MCI, 25% any dementia; age 59±7 years, 56% women). Regardless of biomarker cut-offs, most patients were A−T−N− (54–57%). A+ prevalence was 17–30% (higher with data-driven cut-offs). Up to 13% of all patients (27% of those with MCI and 28% of those with dementia) were potentially eligible for anti-amyloid treatment when AD-consistent CSF was defined as any A+ profile. When A+T+ profile was required, treatment was targeted more to the dementia than MCI stage (eligibility up to 14% in MCI, 22% in dementia). The opposite applied to earlier stage intervention (A+T−N−; eligibility up to 12% in MCI, 2% in dementia).Discussion:In a memory clinic setting with all necessary infrastructure and national guidelines in place for dementia diagnostic examination (“best-case scenario”), most patients did not meet the eligibility criteria for anti-amyloid treatment. Continuing the development of disease-modifying treatments with different mechanisms of action is a priority.

show abstract

Section: Discussionsupporting

confidence: 67%

β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, the Aβ 42 /Aβ 40 ratio was abnormally reduced in both, allowing the diagnosis of AD. Despite some concerns about the interchangeability between Aβ 42 and the Aβ 42 /Aβ 40 ratio in the AT(N) system [64], the ratio shows better diagnostic accuracy compared to Aβ 42 alone [32,65], correlates better with amyloid imaging by positron emission tomography [32], and its better diagnostic performance has been confirmed in pathologically proven cases [32].…”

Section: Discussionmentioning

confidence: 99%

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

et al. 2021

View full text Add to dashboard Cite

Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Cerebrospinal fluid AD biomarker values were collected as previously described ( 8 ) and measured using either ELISA (INNOTEST) or the Lumipulse G1200 system (Fujeribo, Ghent, Belgium) in line with the manufacturer’s procedures. For samples quantified by ELISA, abnormal values were defined as amyloid-β 42 (Aβ 42 ) <500 pg./mL or Aβ 42/40 ratio ≤ 0.05, phosphorylated-tau >60 pg./mL, total-tau >450 pg./mL, according to the cutoff values recommended by the manufacturer, internal data and in the literature ( 8 , 9 ). For samples quantified with Lumipulse, abnormal values were defined as Aβ 42 ≤ 600 pg./mL, or Aβ 42/40 ratio ≤ 0.07, phosphorylated-tau >60 pg./mL, total-tau >450 pg./mL, according to the cutoff values recommended by the manufacturer, and internal data.…”

Section: Methodsmentioning

confidence: 99%

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

Gouilly,

Salabert,

Bertrand

et al. 2023

Front. Neurol.

Self Cite

View full text Add to dashboard Cite

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression.

show abstract

Taking the A Train? Limited Consistency of Aβ42 and the Aβ42/40 Ratio in the AT(N) Classification

Cited by 7 publications

References 14 publications

β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population

β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

Contact Info

Product

Resources

About