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.

Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements / Nerattini M.; Rubino F.; Arnone A.; Polito C.; Mazzeo S.; Lombardi G.; Puccini G.; Nacmias B.; De Cristofaro M.T.; Sorbi S.; Pupi A.; Sciagra R.; Bessi V.; Berti V.. - In: NEUROLOGICAL SCIENCES. - ISSN 1590-1874. - ELETTRONICO. - (2021), pp. 0-0. [10.1007/s10072-021-05704-2]

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

Nerattini M.;Rubino F.;Arnone A.;Polito C.;Mazzeo S.;Lombardi G.;Puccini G.;Nacmias B.;Sorbi S.;Pupi A.;Sciagra R.;Bessi V.;Berti V.
2021

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.
2021
0
0
Nerattini M.; Rubino F.; Arnone A.; Polito C.; Mazzeo S.; Lombardi G.; Puccini G.; Nacmias B.; De Cristofaro M.T.; Sorbi S.; Pupi A.; Sciagra R.; Bessi V.; Berti V.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1259790
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