Traumatic brain injury elevates the Alzheimer's amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury.
The increased risk for Alzheimer's Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influence the development of this age-related dementia. Recently, we have shown that the levels of the beta-amyloid peptide (A beta 1-42) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A beta with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A beta 1-42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific enolase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A beta 1-40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A beta 1-42 and A beta 1-40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in determining the A beta level in CSF after brain injury.
Emmerling
M R
MR
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. mark.emmerling@wl.com
Morganti-Kossmann
M C
MC
Kossmann
T
T
Stahel
P F
PF
Watson
M D
MD
Evans
L M
LM
Mehta
P D
PD
Spiegel
K
K
Kuo
Y M
YM
Roher
A E
AE
Raby
C A
CA
D000209:Acute-Phase Proteins / Q000134:cerebrospinal fluid*; D000544:Alzheimer Disease / Q000453:epidemiology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000150:complications; D015331:Cohort Studies; D016207:Cytokines / Q000134:cerebrospinal fluid*; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D000209:Acute-Phase Proteins; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D010751:Phosphopyruvate Hydratase