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The relationship between CSF biomarkers and cerebral metabolism in early-onset Alzheimer’s disease

  • Alice JaillardEmail author
  • Matthieu Vanhoutte
  • Aurélien Maureille
  • Susanna Schraen
  • Emilie Skrobala
  • Xavier Delbeuck
  • Adeline Rollin-Sillaire
  • Florence Pasquier
  • Stéphanie Bombois
  • Franck Semah
Original Article

Abstract

Purpose

One can reasonably suppose that cerebrospinal spinal fluid (CSF) biomarkers can identify distinct subgroups of Alzheimer’s disease (AD) patients. In order to better understand differences in CSF biomarker patterns, we used FDG PET to assess cerebral metabolism in CSF-based subgroups of AD patients.

Methods

Eighty-five patients fulfilling the criteria for probable early-onset AD (EOAD) underwent lumbar puncture, brain 18F-FDG PET and MRI. A cluster analysis was performed, with the CSF biomarkers for AD as variables. Vertex-wise, partial-volume-corrected metabolic maps were computed for the patients and compared between the clusters of patients. Linear correlations between each CSF biomarker and the metabolic maps were assessed.

Results

Three clusters emerged. The “Aβ42” cluster contained 32 patients with low levels of Aβ42, while tau and p-tau remained within the normal range. The “Aβ42 + tau” cluster contained 41 patients with low levels of Aβ42 and high levels of tau and p-tau. Lastly, the “tau” cluster contained 12 patients with very high levels of tau and p-tau and low-normal levels of Aβ42. There were no inter-cluster differences in age, sex ratio, educational level, APOE genotype, disease duration or disease severity. The “Aβ42 + tau” and “tau” clusters displayed more marked frontal hypometabolism than the “Aβ42” cluster did, and frontal metabolism was significantly negatively correlated with the CSF tau level. The “Aβ42” and “Aβ42 + tau” clusters displayed more marked hypometabolism in the left occipitotemporal region than the “tau” cluster did, and metabolism in this region was significantly and positively correlated with the CSF Aβ42 level.

Conclusion

The CSF biomarkers can be used to identify metabolically distinct subgroups of patients with EOAD. Future research should seek to establish whether these biochemical differences have clinical consequences.

Keywords

FDG-PET Alzheimer’s disease CSF biomarkers 

Notes

Acknowledgements

David Fraser: proofreading of documents in English.

Funding

Our study has not received any funding.

Compliance with ethical standards

Conflict of interest

- Alice Jaillard: Reports no disclosures.

- Matthieu Vanhoutte: Reports no disclosures.

- Stéphanie Bombois: Reports no disclosures.

- Aurélien Maureille: Reports no disclosures.

- Susanna Schraen: Reports no disclosures.

- Emilie Skrobala: Reports no disclosures.

- Xavier Delbeuck: Reports no disclosures.

- Adeline Rollin-Sillaire: Reports no disclosures.

- Florence Pasquier: Reports no disclosures.

- Franck Semah: Reports no disclosures.

Ethical approval

This research was an ancillary study of the COMAJ cohort, which has been approved by the corresponding local investigational review boards (CPP Nord-Ouest I, CPP Paris Pitié-Salpêtrière and CPP Ile-de-France II; reference: 110–05). All participants gave their written, informed consent to participation in the COMAJ study.

Glossary

18F-FDG

fluorine-18 fluorodeoxyglucose

Aβ42

amyloid-beta 1–42

AD

Alzheimer’s disease

CDR-SOB

Clinical Dementia Rating Scale - sum of boxes

CSF

cerebrospinal fluid

EOAD

early-onset Alzheimer’s disease

FAB

Frontal Assessment Battery

FOV

field of view

LOAD

late-onset Alzheimer’s disease

LP

lumbar puncture

MMSE

Mini Mental State Evaluation

MRI

magnetic resonance imaging

NMDA

N-methyl-D-aspartate

OSEM

ordered subset expectation maximization

PET

positron emission tomography

p-tau

tau phosphorylated at threonine 181

PVE

partial volume effect

SD

standard deviation

VAT

Visual Association Test

VOSP

Visual Object and Space Perception

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alice Jaillard
    • 1
    • 2
    Email author
  • Matthieu Vanhoutte
    • 1
  • Aurélien Maureille
    • 3
  • Susanna Schraen
    • 4
  • Emilie Skrobala
    • 3
  • Xavier Delbeuck
    • 3
  • Adeline Rollin-Sillaire
    • 3
  • Florence Pasquier
    • 2
    • 3
  • Stéphanie Bombois
    • 2
    • 3
  • Franck Semah
    • 1
    • 2
  1. 1.Nuclear Medicine DepartmentCHU LilleLilleFrance
  2. 2.Inserm, U1171LilleFrance
  3. 3.Neurology DepartmentCHU LilleLilleFrance
  4. 4.Department of Biology and PathologyCHU LillLilleFrance

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