What are the Most Frequently Impaired Markers of Neurodegeneration in ADNI Subjects?

Article type: Research Article

Authors: Andriuta, Daniela^{a; *} | Moullart, Véronique^b | Schraen, Susanna^c | Devendeville, Agnes^{a; d} | Meyer, Marc-Etienne^b | Godefroy, Olivier^a | for the Alzheimer’s Disease Neuroimaging¹

Affiliations: [a] Department of Neurology and Laboratory of Functional Neurosciences, University Hospital of Amiens, France | [b] Department of Nuclear Medicine, University Hospital of Amiens, France | [c] Department of Biology and Pathology, Lille University Hospital, France | [d] Department of Gerontology, University Hospital of Amiens, France

Correspondence: [*] Correspondence to: Daniela Andriuta, MD, Department of Neurology, Amiens University Hospital, 80054, Amiens, France. Tel.: +33322668240; Fax: +33322668240; E-mail: andriuta.daniela@chu-amiens.fr.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: The aim of this study was to examine the relationship between cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer’s disease (AD) (Aβ1–42, t-tau, and p-tau) and 18Fluorodeoxyglucose positron emission tomography (FDG-PET) hypometabolism in subjects from the Alzheimer’s Disease Neuroimaging Initiative, and specifically to determine which index of neurodegeneration was most frequently affected. The secondary objective was to determine the most frequently hypometabolic region in patients with a CSF AD signature (abnormal Aβ1–42 and abnormal p-tau). We included the 372 subjects (85 normal subjects, 212 patients with mild cognitive impairment, and 75 patients with AD) with a CSF biomarker dosage (Aβ1–42, t-tau, and p-tau) and brain FDG-PET. The relationship between FDG-PET metabolism (in five regions of interest (ROI) known to be damaged in AD) and CSF t-tau and p-tau levels was studied as a function of CSF Aβ1–42 status. FDG-PET hypometabolism and CSF t-tau and p-tau levels were correlated only in patients with an abnormal CSF Aβ1–42 level (t-tau: R2 = 0.044, p = 0.001; p-tau: R2 = 0.02, p = 0.03). In the latter patients, CSF p-tau was the most frequently (p = 0.0001) abnormal neurodegeneration marker (p-tau: 92.8%; FDG-PET: 56.5%; CSF t-tau: 59.1%). Within the five ROI of FDG PET, the angular gyrus metabolism (R2 = 0.149; p = 0.0001) was selected as the most tightly associated with CSF AD signature. The relation between CSF markers of neurodegeneration (p-tau and t-tau) and brain hypometabolism (in FDG-PET) is conditioned by presence of amyloid abnormality. This finding supports the current physiopathological model of AD. P-tau is the most frequently impaired biomarker. Using FDG PET angular gyrus hypometabolism is the most sensitive to CSF-biomarker-defined AD.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, FDG-PET metabolism, neurodegeneration markers, tau

DOI: 10.3233/JAD-150829

Journal: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 793-800, 2016