Cerebrospinal Fluid Levels of Amyloid Beta 1-43 Mirror 1-42 in Relation to Imaging Biomarkers of Alzheimer's Disease.

ABSTRACT: Introduction: Amyloid beta 1-43 (A?43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (A?42). Cerebrospinal fluid (CSF) A?43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF A?43 and established imaging biomarkers of Alzheimer's disease has never been assessed. Materials and Methods: In this observational study, CSF A?43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent ¹⁸F-Flutemetamol PET. Seventy-eight subjects were assessed with ¹⁸F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid A?43 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF A?43 between subjects with ¹⁸F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF A?43 and A?42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF A?43 average rho -0.73, A?42 -0.74. Both CSF A? peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF A?42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF A?43/42 and imaging biomarkers were significantly different for the two A? peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid A?43 appears to be strongly correlated with cerebral amyloid deposits in the same way as A?42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF A?43 performs better than the classical CSF biomarker A?42 for distinguishing SCD and MCI.

SUBMITTER: Almdahl IS 

PROVIDER: S-EPMC5293760 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature