Open AccessCSF A β 42/A β 40 and A β 42/A β 38 ratios: better diagnostic markers of Alzheimer disease
Author(s) -
Janelidze Shorena,
Zetterberg Henrik,
Mattsson Niklas,
Palmqvist Sebastian,
Vanderstichele Hugo,
Lindberg Olof,
Westen Danielle,
Stomrud Erik,
Minthon Lennart,
Blennow Kaj,
Hansson Oskar
Publication year - 2016
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.274
Subject(s) - medicine , cerebrospinal fluid , dementia , vascular dementia , magnetic resonance imaging , pathology , alzheimer's disease , dementia with lewy bodies , positron emission tomography , cognitive decline , disease , gastroenterology , nuclear medicine , radiology
Abstract Objective The diagnostic accuracy of cerebrospinal fluid ( CSF ) biomarkers for Alzheimer's disease ( AD ) must be improved before widespread clinical use. This study aimed to determine whether CSF A β 42/A β 40 and A β 42/A β 38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF A β 42 alone. Methods The study comprised three different cohorts ( n = 1182) in whom CSF levels of A β 42, A β 40, and A β 38 were assessed. CSF A β s were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid ( 18 F‐flutemetamol) positron emission tomography ( PET ) imaging ( n = 215) or clinical diagnosis ( n = 967) of well‐characterized patients. Results When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF A β 42/A β 40 and A β 42/A β 38 ratios were significantly better predictors of abnormal amyloid PET than CSF A β 42. Lower A β 42, A β 42/A β 40, and A β 42/A β 38 ratios, but not A β 40 and A β 38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower A β 38, A β 40, and A β 42, but not the ratios, correlated with non‐ AD ‐specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the A β 42/A β 40 and A β 42/A β 38 ratios showed increased accuracy compared to A β 42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all A β s (including A β 42) were decreased. Interpretation The CSF A β 42/A β 40 and A β 42/A β 38 ratios are significantly better than CSF A β 42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non‐ AD dementias. The ratios reflect AD ‐type pathology better, whereas decline in CSF A β 42 is also associated with non‐AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF A β 42 should be used in the clinical work‐up of AD .