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Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

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Abstract

Background

Alzheimer’s disease (AD) diagnosis can be hindered by amyloid biomarkers discordances.

Objective

We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aβ42 and Aβ42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays.

Method

Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aβ42, Aβ42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans.

Results

Groups were defined basing on the agreement among CSF Aβ42 (A), CSF Aβ42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aβ42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aβ42 results, with Aβ42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis.

Conclusion

The amyloid discordant cases could be overcome by combining CSF Aβ42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aβ42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

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Acknowledgements

Thanks to Fondazione Turati for providing materials for cerebrospinal fluid assay.

Author information

Authors and Affiliations

  1. Nuclear Medicine Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Piero Palagi 1, 50139, Florence, Italy

    Matilde Nerattini, Federica Rubino, Annachiara Arnone, Maria Teresa De Cristofaro, Alberto Pupi, Roberto Sciagrà & Valentina Berti

  2. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence (NEUROFARBA), Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy

    Cristina Polito, Salvatore Mazzeo, Benedetta Nacmias, Sandro Sorbi & Valentina Bessi

  3. IRCCS Fondazione Don Carlo Gnocchi, Via Scandicci 269, 50143, Florence, Italy

    Gemma Lombardi, Benedetta Nacmias & Sandro Sorbi

  4. Department of Nuclear Medicine, Hospital of Prato, Via Suor Niccolina Infermiera, 20/22, 59100, Prato, Italy

    Giulia Puccini

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  1. Matilde Nerattini
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Contributions

Matilde Nerattini: Conceptualization (supporting); writing, original draft preparation (equal); formal analysis (equal); investigation (equal).

Federica Rubino: Conceptualization (supporting); writing, original draft preparation (equal); formal analysis (equal); investigation (equal).

Annachiara ArnoneL Conceptualization (supporting); writing, original draft preparation (equal); formal analysis (equal); investigation (equal).

Cristina Polito: Methodology (equal); writing, review and editing (supporting).

Giulia Puccini: Methodology (equal); writing, review and editing (supporting).

Salvatore Mazzeo: Resources; writing, review and editing (supporting).

Gemma Lombardi: Resources; writing, review and editing (supporting).

Benedetta Nacmias: Resources; writing, review and editing (supporting).

Maria Teresa De Cristofaro: Resources; writing, review and editing (supporting).

Sandro Sorbi: Resources; supervision (supporting); writing, review and editing (supporting).

Alberto Pupi: Writing, review and editing (supporting); supervision (supporting).

Roberto Sciagrà: Writing, review and editing (supporting); supervision (supporting).

Valentina Bessi: Resources; writing, review and editing (supporting).

Valentina Berti: Conceptualization (lead); supervision (lead); writing, original draft (supporting); writing, review and editing (lead).

Corresponding author

Correspondence to Matilde Nerattini.

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Ethics approval

Participants (or their caregivers) gave informed consent for all investigations, and study procedures were approved by the local Institutional Review Board (reference 15691_oss).

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The authors declare that they have no conflicts of interest.

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Nerattini, M., Rubino, F., Arnone, A. et al. Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements. Neurol Sci 43, 2469–2480 (2022). https://doi.org/10.1007/s10072-021-05704-2

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  • DOI: https://doi.org/10.1007/s10072-021-05704-2

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