Figure 1.

Schematic drawing of interstitial fluid (ISF) and cerebrospinal fluid (CSF) sampling of tau protein and amyloid-β (Aβ) peptides following traumatic brain injury (TBI) on a coronal brain section. An external ventricular drainage (EVD) and a microdialysis (MD) catheter are placed into the frontal horn of the ventricular system and superficial cortex, respectively. Initially, TBI results in an accumulation of amyloid precursor protein (APP) that, following its degradation, may lead to intra-axonal amyloid-β (Aβ) accumulation and plaque formation in the brain parenchyma. Following TBI, early Aβ plaques are typically of the diffuse type in contrast to those observed in Alzheimer’s disease whereas dense plaques may be observed in patients surviving for many years post-injury. Alternatively, Aβ peptides may also be produced by normal neuronal activity and be reduced by TBI. Neurofibrillary tangles (NFTs) can also be formed after TBI as a consequence of hyperphosphorylated tau. In humans, NFT formation does not appear to occur acutely and has mainly been observed beyond 4 weeks post-injury following a single, severe TBI. However, hyperphosphorylated tau aggregations can be observed as a characteristic observation following repetitive mild TBI. The question marks illustrate the unknown features of Aβ and tau accumulation, their release into the CSF or ISF, or the dynamic distribution between the CSF and ISF levels of Aβ and tau.