Assessment of 18F-Florbetaben Amyloid PET Imaging in Patients with Suspected Alzheimer’s Disease and Isolated Increase in Cerebrospinal Fluid Tau Proteins

Manca, Chloé; Hopes, Lucie; Kearney‐Schwartz, Anna; Roch, Véronique; Karcher, Gilles; Baumann, Cédric; Marie, Pierre-Yves; Malaplate-Armand, Catherine; Jonveaux, Thérèse Rivasseau; Verger, Antoine

doi:10.3233/jad-181146

Cited by 6 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our cross-sectional and longitudinal analyses in this large cohort provided evidence for the existence of an additional alternative pathway, where [18F]Florbetapir PET became abnormal first. Firstly, and consistent with previous reports [ 6 – 8 , 13 – 15 , 17 , 18 , 20 – 32 , 34 ] (Supplementary Table 1 ), we observed isolated [18F]Florbetapir PET positivity in a non-negligible percentage of cases. This cross-sectional evidence alone questions whether isolated CSF amyloid-β 42 positivity represents the only possible pathway toward fully abnormal amyloid-β biomarkers.…”

Section: Discussionsupporting

confidence: 93%

Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

et al. 2020

View full text Add to dashboard Cite

Mismatch between CSF and PET amyloid-β biomarkers occurs in up to ≈20% of preclinical/prodromal Alzheimer’s disease individuals. Factors underlying mismatching results remain unclear. In this study we hypothesized that CSF/PET discordance provides unique biological/clinical information. To test this hypothesis, we investigated non-demented and demented participants with CSF amyloid-β42 and [18F]Florbetapir PET assessments at baseline (n = 867) and at 2-year follow-up (n = 289). Longitudinal trajectories of amyloid-β positivity were tracked simultaneously for CSF and PET biomarkers. In the longitudinal cohort (n = 289), we found that participants with normal CSF/PET amyloid-β biomarkers progressed more frequently toward CSF/PET discordance than to full CSF/PET positivity (χ2(1) = 5.40; p < 0.05). Progression to CSF+/PET+ status was ten times more frequent in cases with discordant biomarkers, as compared to csf−/pet− cases (χ2(1) = 18.86; p < 0.001). Compared to the CSF+/pet− group, the csf−/PET+ group had lower APOE-ε4ε4 prevalence (χ2(6) = 197; p < 0.001; n = 867) and slower rate of brain amyloid-β accumulation (F(3,600) = 12.76; p < 0.001; n = 608). These results demonstrate that biomarker discordance is a typical stage in the natural history of amyloid-β accumulation, with CSF or PET becoming abnormal first and not concurrently. Therefore, biomarker discordance allows for identification of individuals with elevated risk of progression toward fully abnormal amyloid-β biomarkers, with subsequent risk of neurodegeneration and cognitive decline. Our results also suggest that there are two alternative pathways (“CSF-first” vs. “PET-first”) toward established amyloid-β pathology, characterized by different genetic profiles and rates of amyloid-β accumulation. In conclusion, CSF and PET amyloid-β biomarkers provide distinct information, with potential implications for their use as biomarkers in clinical trials.

show abstract

Section: Discussionsupporting

confidence: 93%

Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

et al. 2020

View full text Add to dashboard Cite

show abstract

“…By contrast, the risk of AD would remain significant in patients in whom Aß42 concentrations are normal but close to the abnormal range (from 600 to 843 pg/mL in the present study), especially when associated with mild neurocognitive disorders and an increase in CSF P-tau proteins [16]. This was indeed the case of 10 patients herein among whom 1 had a definitely negative amyloid PET although 9 had not (Figure 1).…”

Section: This Relationship Between Aß42 Concentration and Amyloid Petsupporting

confidence: 47%

“…Alzheimer's Disease and Related Disorders Association (NINCDS ADRDA) criteria [13,14], 25 exhibited an increase in CSF P-tau concentrations (>60 pg/mL) along with normal Aß42 concentration (>600 pg/mL) and Aß42/Aß40 ratio (>0.07), according to routine cut-off values [3,15]. The patients presenting this CSF biomarker profile were included in this ancillary analysis of the MAF (Maladie d'Alzheimer Florbetaben) study (NCT02556502) [16] with the following main additional inclusion criteria: age ≥18 years old, absence of formal or relative contraindication to 18 F-florbetaben PET, affiliation to a health care system, no guardianship or curatorship, and absence of pregnancy. In addition, patients unable to undergo 18 F-florbetaben PET due to agitation or confusion, as well as those unable to sign the informed consent form, were not included.…”

Section: National Institute Of Neurological and Communicative Disordementioning

confidence: 99%

Amyloid PETs are commonly negative in suspected Alzheimer’s disease with an increase in CSF phosphorylated-tau protein concentration but an Aβ42 concentration in the very high range: a prospective study

et al. 2019

Self Cite

View full text Add to dashboard Cite

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

show abstract

Aβ Imaging in Aging, Alzheimer’s Disease, and Other Neurodegenerative Conditions

Villemagne¹,

Doré²,

Burnham³

et al. 2020

PET and SPECT in Neurology

View full text Add to dashboard Cite

Assessment of 18F-Florbetaben Amyloid PET Imaging in Patients with Suspected Alzheimer’s Disease and Isolated Increase in Cerebrospinal Fluid Tau Proteins

Cited by 6 publications

References 25 publications

Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

Longitudinal pathways of cerebrospinal fluid and positron emission tomography biomarkers of amyloid-β positivity

Amyloid PETs are commonly negative in suspected Alzheimer’s disease with an increase in CSF phosphorylated-tau protein concentration but an Aβ42 concentration in the very high range: a prospective study

Aβ Imaging in Aging, Alzheimer’s Disease, and Other Neurodegenerative Conditions

Contact Info

Product

Resources

About