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Plasma β-Amyloid 1-42/1-40 Ratio Provides Insight into the Presence of Alzheimer’s Disease.

Abstract ID: 32570

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Keith R Morneau, ALM1; Brian G Sansoucy, MBA1; Robert J Lagier, MS2; Charles M Rowland, MS2; Torey Neusch, BS1; Altin Qeleshi, MS1; Edward I Ginns, MD, PhD1 and Nigel J Clarke, PhD3, (1)Quest Diagnostics, Marlborough, MA, USA, (2)Quest Diagnostics, Alameda, CA, USA, (3)Quest Diagnostics, San Juan Capistrano, CA, USA

Background: Somatic genetic recombination of the amyloid precursor protein (APP) has been implicated in neuronal functions (e.g., plasticity and synaptic wiring) that contribute to learning, memory, and cognition. Ironically, secretase-mediated cleavage of this protein yields 2 peptides (β-amyloids 1-42 and 1-40) implicated in Alzheimer disease (AD). Measurement of β-amyloid 1-42, as well as the Tau and hyperphosphorylated Tau proteins, in cerebral spinal fluid (CSF) has become an established parameter in considering a diagnosis of AD. However, because of the invasive method of obtaining CSF, the existence of blood-based biomarkers could enhance the screening process of those likely to be affected by this disease. Method: We have developed and validated a multiplex assay for the simultaneous measurement of β-amyloid 1-42 and 1-40 peptides in plasma with a high level of analytical sensitivity. We used this assay to analyze 100 plasma specimens from patients who were pre-characterized as normal (n=35) or having early MCI (mild cognitive impairment) (n=25), late MCI (n=15), or AD (n=25) according to the CDR (Clinical Dementia Rating) and the MOCA (Montreal Cognitive Assessment) tests. The 1-42/1-40 ratio was calculated for each specimen. Result: A statistically significant difference (P = 0.008, Kruskal-Wallis H test) was found between the normal and AD-affected samples when considering ratios. These data suggest clinical specificity of 71% and sensitivity of 76% for differentiating normal from AD-affected individuals. When pairing late MCI with AD-affected, and pairing early MCI with normal specimens, a slight statistical improvement was observed. Conclusion: We developed a method that simultaneously measures β-amyloid peptides 1-42 and 1-40 in plasma specimens. This method can be used to assess the 1-42/1-40 ratio, which may be useful as part of a screening process for identifying patients with late MCI or AD.