The relationship between CSF biomarkers and cerebral metabolism in early-onset Alzheimer’s disease
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.
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.
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.
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.
KeywordsFDG-PET Alzheimer’s disease CSF biomarkers
David Fraser: proofreading of documents in English.
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.
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.
Clinical Dementia Rating Scale - sum of boxes
early-onset Alzheimer’s disease
Frontal Assessment Battery
field of view
late-onset Alzheimer’s disease
Mini Mental State Evaluation
magnetic resonance imaging
ordered subset expectation maximization
positron emission tomography
tau phosphorylated at threonine 181
partial volume effect
Visual Association Test
Visual Object and Space Perception
- 13.McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.CrossRefGoogle Scholar
- 19.Deloche, G, Hannequin D.. DO 80, Epreuve de dénomination orale d'images [DO80: Eighty pictures: confrontation oral naming battery], 1997 Paris Les Editions du Centre de Psychologie.Google Scholar
- 21.Vercruysse O, Paquet C, Gabelle A, Delbeuck X, Blanc F, Wallon D, et al. Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF biomarkers. Curr Alzheimer Res. 2018.Google Scholar
- 45.Alvarez JA, Emory E. Executive function and the frontal lobes: a meta-analytic review. Neuropsychol Rev. 2006;16:17–42.Google Scholar