Microdialysis monitoring of Amyloid β isoforms - potential biomarkers for diffuse axonal injury after severe traumatic brain injury

Severe traumatic brain injury (TBI), defined as patients with a Glasgow Coma Scale (GCS) score ≤ 8, is a well-known cause of life-long disability and death. TBI is commonly observed in young adults although the incidence of elderly people is increasing. TBI has also been identified as an important environmental risk factor for the development of Alzheimer ́s disease (AD) later in life. Amyloid-β (Aβ) peptide, believed to play a central role in the development of both familial and late-onset AD, can be detected in the human brain using intracerebral microdialysis (MD) in the early post-injury after TBI. The aim of this study was to further evaluate whether Aβ40 and Aβ42 could be detected after severe TBI by intracerebral microdialysis, since these peptides are of particular interest as potential biomarkers for diffuse axonal injury (DAI). We evaluated 10 patients with severe TBI up to 4 days post-injury using MD to sample interstitial Aβ peptides later analyzed using the Luminex xMAP technique allowing analysis of two-hour fractions. The Aβ results were compared to markers for cerebral energy metabolism (glucose, lactate, pyruvate, glycerol, glutamate), CT-scans and clinical factors. We found that interstitial Aβ-40 and Aß-42 levels were consistently higher in the DAI group compared to the focal injury group day 16 postinjury, being significantly increased at 9798 and 113-116 hours post-injury (p <0.05). These results indicate that Aβ-40 and Aß-42 might be important biomarkers for axonal injury and their detection using microdialysis can help us better understand the dynamics of axonal injury mechanisms in the injured human brain.