Traumatic brain injury (TBI) survivors frequently suffer from life-long deficits 
in cognitive functions and a reduced quality of life. Axonal injury, observed in 
many severe TBI patients, results in accumulation of amyloid precursor protein 
(APP). Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ) 
peptides, a hallmark finding in Alzheimer's disease (AD). At autopsy, brains of 
AD and a subset of TBI victims display some similarities including accumulation 
of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. 
Most epidemiological evidence suggests a link between TBI and AD, implying that 
TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as 
biomarkers in interstitial fluid (ISF) using cerebral microdialysis and/or 
cerebrospinal fluid (CSF) following clinical TBI. In the present review, the 
available clinical and experimental literature on Aβ peptides and tau as 
potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and 
ISF tau protein levels have been observed following severe TBI and suggested to 
correlate with clinical outcome. Although Aβ peptides are produced by normal 
neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be 
neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to 
neuronal activity and/or the presence of axonal injury. The heterogeneity of 
animal models, clinical cohorts, analytical techniques, and the complexity of 
TBI in the available studies make the clinical value of tau and Aβ as biomarkers 
uncertain at present. Additionally, the link between early post-injury changes 
in tau and Aβ peptides and the future risk of developing AD remains unclear. 
Future studies using methods such as rapid biomarker sampling combined with 
enhanced analytical techniques and/or novel pharmacological tools could provide 
additional information on the importance of Aβ peptides and tau protein in both 
the acute pathophysiology and long-term consequences of TBI.