CSF A?42/A?40 and A?42/A?38 ratios: better diagnostic markers of Alzheimer disease.

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?42/A?40 and A?42/A?38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF A?42 alone.

Methods

The study comprised three different cohorts (n = 1182) in whom CSF levels of A?42, A?40, and A?38 were assessed. CSF A?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?42/A?40 and A?42/A?38 ratios were significantly better predictors of abnormal amyloid PET than CSF A?42. Lower A?42, A?42/A?40, and A?42/A?38 ratios, but not A?40 and A?38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower A?38, A?40, and A?42, but not the ratios, correlated with non-AD-specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the A?42/A?40 and A?42/A?38 ratios showed increased accuracy compared to A?42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all A?s (including A?42) were decreased.

Interpretation

The CSF A?42/A?40 and A?42/A?38 ratios are significantly better than CSF A?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?42 is also associated with non-AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF A?42 should be used in the clinical work-up of AD.

SUBMITTER: Janelidze S 

PROVIDER: S-EPMC4774260 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature