Neurodegeneration biomarkers for diagnosis of Alzheimer’s and MND

A portfolio of CSF biomarkers corresponding to different stages of the neurodegenerative process aids the diagnosis of Alzheimer’s disease (AD) and motor neuron diseases (MND). The classic AD markers beta amyloid and tau measure aggregates like plaques and tangles. The most reliable measure of amyloid pathology is the ratio of beta amyloid 1-42 to 1-40, which takes into account the patient’s individual amyloid level. Total tau (T-tau) is an indicator of unspecific neuronal damage, while phosphorylated tau (P-tau) is AD specific. Determination of new synaptic biomarkers like BACE1 and neurogranin can indicate when synaptic integrity and hence cognitive function is impaired. In addition, analysis of the genetic risk factor APOE aids the differential and early diagnosis of AD. Neurofilament is an upcoming marker for MND, especially amyotropic lateral sclerosis (ALS). Analysis of the phosphorylated neurofilament heavy (pNf-H) or neurofilament light (Nf-L) subunit enables discrimination of MND from AD. The protein biomarkers beta amyloid 1-42, beta amyloid 1-40, T-tau or P-tau, BACE-1, neurogranin (truncated p75 form) and pNf-H can be determined in patient CSF using a panel of ELISAs developed by EUROIMMUN AG in collaboration with ADx NeuroSciences. The ELISAs use a matrix-independent approach which ensures high consistency in results. The protocols are aligned, require only four hours and are fully automatable. Lyophilized calibrators and controls provide convenient test performance, high precision and clinical accuracy. Genotyping in AD can be carried out using DNA microarrays such as the EUROArray APOE Direct, which determines the variants ε2, ε3 and ε4 in parallel in whole blood samples with fully automated data evaluation. Further tests for neurodegenerative diseases are on the horizon, including additional parameters for AD and MND, biomarkers for Parkinson’s disease (e.g. alpha-synuclein) and indicators of traumatic brain injury.


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