Plasma amyloid-β peptide ratio predicts Alzheimer’s disease
MedWire News: The ratio of plasma amyloid-β (Aβ) peptides, rather than levels of individual peptides, may predict the development of Alzheimer's disease (AD) and dementia, show results from a systematic review and meta-analysis.
It is widely believed that preclinical administration of novel therapeutic agents for dementia - expected to be developed in the coming years - will be the optimal time, ie, before patients develop full dementia or AD, explain Alain Koyama (University of California, San Francisco, USA) and colleagues in the Archives of Neurology.
Thus, preclinical prediction of these conditions is important and critical to effective intervention.
Plasma levels of Aβ peptides have been the main focus of the growing literature on blood-based biomarkers for dementia, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data, the researchers note.
To address this, they conducted a systematic review and meta-analysis of prospective studies published between 1995 and 2011 that measured at least one relevant plasma amyloid-β species (Aβ40, Aβ42, or Aβ42:Aβ40 ratio) and reported risk estimates for the development of dementia, AD, or cognitive decline.
Thirteen studies with a total of 10,303 individuals were included in the analysis.
Koyama et al report that plasma levels of Aβ40 and Aβ42 alone were not significant predictors for dementia or AD risk.
By contrast, patients with the lowest Aβ42:Aβ40 ratios (defined as the lowest quantile in each study) had a significantly increased risk for developing AD (summary risk ratio=1.60) and dementia (risk ratio=1.67) compared with those with the highest ratios.
The researchers say that the findings did not change significantly when they used only data from the most extensively adjusted models reported, when they analyzed the data as continuous levels rather than as ordered categories, or when a single study comprising an all-male cohort was excluded.
Moreover, results from three of four studies reporting using cognitive decline as an outcome were consistent with the meta-analysis in observing that a lower ratio of Aβ42:Aβ40 predicted worse cognitive decline.
The researchers note that there was significant heterogeneity among the studies, which could not be explained by participants' age, gender distribution, the study's follow-up time, or year of publication.
They suggest that such heterogeneity may be due to the wide variety of methods used to measure plasma Aβ, and call for further research in to this issue before plasma Aβ is used more broadly as a predictive biomarker of impending dementia.
"Collectively, the existing research offers cautious support of the hypothesis that lower levels of the plasma Aβ42:Aβ40 ratio reflect a process of selective deposition of Aβ42 in the brain as insoluble amyloid plaques, thus predictive of dementia development," Koyama et al conclude.
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By Laura Cowen