Amyloid-beta (1-42) CSF ELISA

Over the last 15 years measuring Amyloid–beta (1–42) peptide has gained acceptance as a tool to aid in the diagnosis of Alzheimer´s disease. Yet, clinical sensitivity and specificity usually is less than 85%. This can be largely attributed to the Gaussian distribution of Amyloid–beta production in the population. It leads to false positives in the group of "low" Abeta producers and to false negatives in the group of "high" Abeta producers. Normalizing the Amyloid–beta (1–42) values to the most abundant and stably produced Abeta (1–40) isoform overcomes this limitation and significantly improves the diagnostic value to well above 90%. IBL International has set its goal to develop high quality immunoassays for convenient and accurate measurement of Amyloid–beta (1–40) and Amyloid–beta (1–42) in CSF for optimal ratio Determination as can be seen by excellent cross reactivity data of both assays (Table 1)

Both Assays show excellent inter– and intra–assay CVs (Table 2) and inter–lot CVs (Table 3) profiles due to internal quality control standards.

Method comparison with commercially available Amyloid–beta (1–40) ELISA: R²=0.944

Method comparison with commercially availableAmyloid–beta (1–42) ELISA: R² =0.9492

To clinically validate the assays an external study was done at the "Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar der Technischen Universität München, München, Germany" with overall83 clinically known samples. The ratio of both assay values shows highclinical sensitivity and specificity

Amyloid–beta (1–42) ⁄ Amyloid–beta (1–40) ratio superior to Amyloid–beta (1–42) alone

Similar results were obtained by Prof. Dr. med. Piotr Lewczuk, Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, Erlangen, Germany. (to be published soon)

Excerpt from the Instructions for Use

In 2010, the number of dementia patients worldwide was estimated at 36 million. Assuming an ongoing lack of sufficient preventive and curative treatments, this is expected to double every 20 years. Alzheimer’s Disease accounts for roughly 60-70% of all dementia cases. Both prevalence and incidence increase with age. Prevalence is around 1% in those aged 65-69, and more than 30% in those aged 90 or older.

The development of the Disease is characterized by three stages, as defined by the US National Institute on Aging workgroups. A preclinical stage of Alzheimer’s Disease, the mild cognitive impairment (MCI) stage due to AD, and the dementia stage due to AD [9-11]. Amyloidosis occurs as early as the preclinical stage. The first cognitive deficits can manifest themselves in MCI stage, while in the dementia stage patients are unable to do any work or daily chores.

The concentration of amyloid-beta (1-42) is therefore recognized as a useful biomarker (in combination with other biomarkers such as Tau and Phospho-Tau) in diagnosing Alzheimer’s Disease. Moreover, a number of independent studies (for example [3-5]) showed the ratio of amyloid-beta (1-42) to amyloid-beta (1-40) to be a superior diagnostic marker for Alzheimer’s Disease.