Marion Tible1, Åsa Sandelius2,3, Kina Höglund2,3, Ann Brinkmalm2,3, Emmanuel Cognat1,4, Julien Dumurgier1,4, Henrik Zetterberg2,3, Jacques Hugon1,4, Claire Paquet5,4, Kaj Blennow2,3. 1. Université de Paris INSERM U1144 F-75010 Paris. 2. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 3. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 4. Center of Cognitive Neurology Lariboisière Fernand-Widal Hospital, APHP, Paris. 5. Université de Paris INSERM U1144 F-75010 Paris claire.paquet@inserm.fr.
Abstract
OBJECTIVE: To assess the ability of a combination of synaptic CSF biomarkers to separate AD and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases. METHODS: Retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25 aa40, synaptotagmin-1) and AD biomarkers were blindly quantified using ELISA or mass spectrometry. Statistical analysis compared CSF levels between various groups AD dementias n=81, MCI-AD n=30, other MCI n=49, other dementias (OD) n=49, neurological controls n=35) as well as their discriminatory powers. RESULTS: All synaptic biomarkers were significantly increased in MCI-AD and AD -dementias patients compared to other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate MCI-AD from controls (AUC ≥0.85) and AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP 25aa40 had the highest discriminative power (AUC=0.93) between AD dementias and controls or OD, and AUC=0.90 between MCI-AD and controls. Higher levels were associated with two alleles of apolipoprotein E (APOE) ε4. CONCLUSION: All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF positive patients from non-AD patients and neurological controls in this cohort. CLASSIFICATION OF EVIDENCE: This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from non-AD patients.
OBJECTIVE: To assess the ability of a combination of synaptic CSF biomarkers to separate AD and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases. METHODS: Retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25 aa40, synaptotagmin-1) and AD biomarkers were blindly quantified using ELISA or mass spectrometry. Statistical analysis compared CSF levels between various groups AD dementias n=81, MCI-AD n=30, other MCI n=49, other dementias (OD) n=49, neurological controls n=35) as well as their discriminatory powers. RESULTS: All synaptic biomarkers were significantly increased in MCI-AD and AD -dementias patients compared to other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate MCI-AD from controls (AUC ≥0.85) and AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP 25aa40 had the highest discriminative power (AUC=0.93) between AD dementias and controls or OD, and AUC=0.90 between MCI-AD and controls. Higher levels were associated with two alleles of apolipoprotein E (APOE) ε4. CONCLUSION: All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF positive patients from non-ADpatients and neurological controls in this cohort. CLASSIFICATION OF EVIDENCE: This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from non-ADpatients.
Authors: Alfredo Ramos-Miguel; Andrea A Jones; Vladislav A Petyuk; Vilte E Barakauskas; Alasdair M Barr; Sue E Leurgans; Philip L De Jager; Kaitlin B Casaletto; Julie A Schneider; David A Bennett; William G Honer Journal: Acta Neuropathol Date: 2021-03-01 Impact factor: 17.088
Authors: Omar H Butt; Justin M Long; Rachel L Henson; Elizabeth Herries; Courtney L Sutphen; Anne M Fagan; Carlos Cruchaga; Jack H Ladenson; David M Holtzman; John C Morris; Beau M Ances; Suzanne E Schindler Journal: Neurobiol Aging Date: 2021-02-11 Impact factor: 5.133