According to a recent study, beta-amyloid plaques are not only a trait of Alzheimer disease, but they are also found in up to 30% of patients who die with acute traumatic brain injury, in which they occur largely in gray matter. Following traumatic brain injury, the beta-amyloid deposition seen in "normal" aging may be consequently sped up, but it has been difficult to measure amyloid binding in vivo.
The main objective of the study was to image amyloid deposition in patients with traumatic brain injury using carbon 11-labeled Pittsburgh compound B ([11C]PiB) PET and to confirm these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in tissue obtained at autopsy.
At a tertiary neuroscience referral center, participants went through imaging of amyloid deposition using [11C]PiB PET. Eleven control patients with an average age of 35 years (range, 24-60 years) and 15 patients with an average age of 33 years (range, 21-50 years) were imaged between 1 and 361 days following traumatic brain injury.
The researchers also conducted [3H]PiB autoradiography and immunocytochemistry for beta-amyloid and a beta-amyloid precursor protein on autopsy-acquired brain tissue from a neuropathology archive.
These samples were taken from 16 patients who died at an average age of 46 years (range, 21-70 years) between 3 hours and 56 days following a traumatic brain injury, and from 7 controls with an average age of 61 years (range, 29-71 years) who died of other causes.
When compared with controls, patients with traumatic brain injury had considerably increased [11C]PiB distribution volume ratios in the cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions corresponding to areas of amyloid deposition seen on immunocytochemistry. In the white matter, immunocytochemistry revealed beta-amyloid and beta-amyloid precursor protein, but no [3H]PiB binding.
Cerebellar gray matter in autopsy-acquired tissue from either controls or patients with traumatic brain injury did not reveal any plaque-associated amyloid immunoreactivity or [3H]PiB binding. However, a single sample of cerebellar tissue from a patient with traumatic brain injury showed amyloid angiopathy affecting meningeal vessels.
The limitations of this study include a small sample size and the absence of serial imaging. Nonetheless, following traumatic brain injury, [11C]PiB demonstrated increased binding in the cortical gray matter and the striatum that is exact, as represented by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with traumatic brain injury. PiB binding seems to be moderately sensitive as well as specific at detecting beta-amyloid plaque, with no instances of false-positive [3H]PiB binding in tissue in which no plaque was present.
The dsicoveries of this study point out that [11C]PiB PET could potentially be of significance in imaging amyloid deposition after traumatic brain injury. Future studies could use serial [11C]PiB PET to follow the course of amyloid deposition and clearance after traumatic brain injury, and could also analyze beta-amyloid deposition in traumatic brain injury in the context of cognitive function and host genotype, particularly apolipoprotein E.
The early binding of [11C]PiB in the striatum of patients with traumatic brain injury is similar to that seen in patients who have mutations in the presenelin-1 gene associated with overproduction of beta-amyloid (particularly beta-amyloid 42) in early-onset forms of Alzheimer disease. This finding further strengthens previously noted links in the pathophysiology underlying Alzheimer disease and traumatic brain injury.