Small study: TBI leads to rapid deposition of brain amyloid

Brain imaging of patients with traumatic brain injury in conjunction with analyses of postmortem tissue appears to confirm that beta amyloid plaques form in some areas of the brain shortly after injury, according to findings published Nov. 11 in JAMA Neurology.

The finding suggests that PET with Pittsburgh compound B (PiB), which binds to amyloid beta plaques, could be useful in the post-TBI patient workup, reported Young T. Hong, Ph.D., of the Wolfson Brain Imaging Centre at the University of Cambridge, England, and colleagues.

"The use of [PET PiB] for amyloid imaging following TBI provides us with the potential for understanding the pathophysiology of TBI, for characterizing the mechanistic drivers of disease progression or suboptimal recovery in the subacute phase of TBI, for identifying patients at high risk of accelerated [Alzheimer’s disease], and for evaluating the potential of antiamyloid therapies," the investigators wrote (JAMA Neurol. 2013 Nov. 11 [doi:10.1001/jamaneurol.2013.4847]).

PET with PiB in 15 patients with a traumatic brain injury that occurred 1-361 days before showed more amyloid binding than did the scans of 11 healthy controls. Amyloid tended to appear rapidly – within 48 hours of injury in some patients. It was located with significantly greater concentration in the cortical gray matter and striatum of TBI patients, compared with controls, but not in the thalamus or white matter. However, most patients showed very little accumulation around the injury site or in places with high vasogenic edema. The medial temporal and hippocampal regions were likewise spared, the investigators noted.

They saw similar results in comparisons of postmortem tissue samples from 16 patients who had died 3 hours to 56 days after a TBI and 7 who had died of other, nonneurologic causes that were analyzed via autoradiography with tritium-labeled PiB and immunocytochemistry for amyloid beta. TBI patients had more frequent and denser amyloid in the neocortical gray matter than did controls. There was no cerebellar cortical amyloid binding among TBI patients except for a 61-year old woman who died 12 hours after a brain injury and had amyloid accumulation in the meningeal vessels.

In the imaging portion of the study, TBI patients and healthy controls had median ages of 33 years and 35 years, respectively. The postmortem analyses involved TBI patients and controls with median ages of 46 years and 61 years, respectively. Patients were matched for age within the cohorts.

Of the 15 TBI patients who underwent PET with PiB, 8 survived with good recovery, 2 with moderate disability, and 3 with severe disability; the other 2 remained in a vegetative state.

The amyloid biding in the TBI patients is reminiscent of the early amyloid deposition seen in some patients who have presenilin-1 gene mutations, which cause early-onset Alzheimer’s disease. The areas of PiB binding in the TBI patients "would therefore be concordant with currently proposed mechanism of overproduction leading to amyloid deposition in TBI," the authors noted.

The study’s biggest weaknesses are its small sample size and lack of serial imaging, the latter perhaps most important because the small proportion of late studies in the 15-patient cohort "limits inferences regarding the temporal pattern of [PiB] binding in vivo and requires confirmation in a larger cohort," they wrote.

The National Institute for Health Research Cambridge Biomedical Research Centre funded the study. Two authors – Dr. William E. Klunk and Chester A. Mathis, Ph.D. – are coinventors of PiB and have a financial interest in the licensing agreement for PiB between GE Healthcare and the University of Pittsburgh.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

Brain imaging of patients with traumatic brain injury in conjunction with analyses of postmortem tissue appears to confirm that beta amyloid plaques form in some areas of the brain shortly after injury, according to findings published Nov. 11 in JAMA Neurology.

The finding suggests that PET with Pittsburgh compound B (PiB), which binds to amyloid beta plaques, could be useful in the post-TBI patient workup, reported Young T. Hong, Ph.D., of the Wolfson Brain Imaging Centre at the University of Cambridge, England, and colleagues.

"The use of [PET PiB] for amyloid imaging following TBI provides us with the potential for understanding the pathophysiology of TBI, for characterizing the mechanistic drivers of disease progression or suboptimal recovery in the subacute phase of TBI, for identifying patients at high risk of accelerated [Alzheimer’s disease], and for evaluating the potential of antiamyloid therapies," the investigators wrote (JAMA Neurol. 2013 Nov. 11 [doi:10.1001/jamaneurol.2013.4847]).

PET with PiB in 15 patients with a traumatic brain injury that occurred 1-361 days before showed more amyloid binding than did the scans of 11 healthy controls. Amyloid tended to appear rapidly – within 48 hours of injury in some patients. It was located with significantly greater concentration in the cortical gray matter and striatum of TBI patients, compared with controls, but not in the thalamus or white matter. However, most patients showed very little accumulation around the injury site or in places with high vasogenic edema. The medial temporal and hippocampal regions were likewise spared, the investigators noted.

They saw similar results in comparisons of postmortem tissue samples from 16 patients who had died 3 hours to 56 days after a TBI and 7 who had died of other, nonneurologic causes that were analyzed via autoradiography with tritium-labeled PiB and immunocytochemistry for amyloid beta. TBI patients had more frequent and denser amyloid in the neocortical gray matter than did controls. There was no cerebellar cortical amyloid binding among TBI patients except for a 61-year old woman who died 12 hours after a brain injury and had amyloid accumulation in the meningeal vessels.

In the imaging portion of the study, TBI patients and healthy controls had median ages of 33 years and 35 years, respectively. The postmortem analyses involved TBI patients and controls with median ages of 46 years and 61 years, respectively. Patients were matched for age within the cohorts.

Of the 15 TBI patients who underwent PET with PiB, 8 survived with good recovery, 2 with moderate disability, and 3 with severe disability; the other 2 remained in a vegetative state.

The amyloid biding in the TBI patients is reminiscent of the early amyloid deposition seen in some patients who have presenilin-1 gene mutations, which cause early-onset Alzheimer’s disease. The areas of PiB binding in the TBI patients "would therefore be concordant with currently proposed mechanism of overproduction leading to amyloid deposition in TBI," the authors noted.

The study’s biggest weaknesses are its small sample size and lack of serial imaging, the latter perhaps most important because the small proportion of late studies in the 15-patient cohort "limits inferences regarding the temporal pattern of [PiB] binding in vivo and requires confirmation in a larger cohort," they wrote.

The National Institute for Health Research Cambridge Biomedical Research Centre funded the study. Two authors – Dr. William E. Klunk and Chester A. Mathis, Ph.D. – are coinventors of PiB and have a financial interest in the licensing agreement for PiB between GE Healthcare and the University of Pittsburgh.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

Brain imaging of patients with traumatic brain injury in conjunction with analyses of postmortem tissue appears to confirm that beta amyloid plaques form in some areas of the brain shortly after injury, according to findings published Nov. 11 in JAMA Neurology.

The finding suggests that PET with Pittsburgh compound B (PiB), which binds to amyloid beta plaques, could be useful in the post-TBI patient workup, reported Young T. Hong, Ph.D., of the Wolfson Brain Imaging Centre at the University of Cambridge, England, and colleagues.

"The use of [PET PiB] for amyloid imaging following TBI provides us with the potential for understanding the pathophysiology of TBI, for characterizing the mechanistic drivers of disease progression or suboptimal recovery in the subacute phase of TBI, for identifying patients at high risk of accelerated [Alzheimer’s disease], and for evaluating the potential of antiamyloid therapies," the investigators wrote (JAMA Neurol. 2013 Nov. 11 [doi:10.1001/jamaneurol.2013.4847]).

PET with PiB in 15 patients with a traumatic brain injury that occurred 1-361 days before showed more amyloid binding than did the scans of 11 healthy controls. Amyloid tended to appear rapidly – within 48 hours of injury in some patients. It was located with significantly greater concentration in the cortical gray matter and striatum of TBI patients, compared with controls, but not in the thalamus or white matter. However, most patients showed very little accumulation around the injury site or in places with high vasogenic edema. The medial temporal and hippocampal regions were likewise spared, the investigators noted.

They saw similar results in comparisons of postmortem tissue samples from 16 patients who had died 3 hours to 56 days after a TBI and 7 who had died of other, nonneurologic causes that were analyzed via autoradiography with tritium-labeled PiB and immunocytochemistry for amyloid beta. TBI patients had more frequent and denser amyloid in the neocortical gray matter than did controls. There was no cerebellar cortical amyloid binding among TBI patients except for a 61-year old woman who died 12 hours after a brain injury and had amyloid accumulation in the meningeal vessels.

In the imaging portion of the study, TBI patients and healthy controls had median ages of 33 years and 35 years, respectively. The postmortem analyses involved TBI patients and controls with median ages of 46 years and 61 years, respectively. Patients were matched for age within the cohorts.

Of the 15 TBI patients who underwent PET with PiB, 8 survived with good recovery, 2 with moderate disability, and 3 with severe disability; the other 2 remained in a vegetative state.

The amyloid biding in the TBI patients is reminiscent of the early amyloid deposition seen in some patients who have presenilin-1 gene mutations, which cause early-onset Alzheimer’s disease. The areas of PiB binding in the TBI patients "would therefore be concordant with currently proposed mechanism of overproduction leading to amyloid deposition in TBI," the authors noted.

The study’s biggest weaknesses are its small sample size and lack of serial imaging, the latter perhaps most important because the small proportion of late studies in the 15-patient cohort "limits inferences regarding the temporal pattern of [PiB] binding in vivo and requires confirmation in a larger cohort," they wrote.

The National Institute for Health Research Cambridge Biomedical Research Centre funded the study. Two authors – Dr. William E. Klunk and Chester A. Mathis, Ph.D. – are coinventors of PiB and have a financial interest in the licensing agreement for PiB between GE Healthcare and the University of Pittsburgh.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal