2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Brain-Injuries

To image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue.. In vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for β-amyloid (Aβ) and β-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes.. We quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aβ and β-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue.. Compared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aβ and β-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels.. [11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.

Topics: Adult; Aged; Amyloid beta-Peptides; Aniline Compounds; Brain; Brain Injuries; Carbon Radioisotopes; Cohort Studies; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Thiazoles; Time Factors; Tritium; Young Adult

Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD) and amyloid β (Aβ) deposition is observed histopathologically in the traumatized brain. This study was conducted to detect cerebral Aβ deposition using amyloid positron emission tomography (PET) in patients with neuropsychological impairment after TBI.. Twelve patients with post-traumatic neuropsychological impairment (11 men and one woman, age range = 21-78 years) were examined using Pittsburgh Compound B ((11)C-PIB) PET at the chronic stage after TBI (range = 5-129 months).. (11)C-PIB was positive in three patients and negative in the other nine patients. There was no correlation between (11)C-PIB deposition and the severity of injury; initial CT findings; elapsed time from the injury; and neuropsychological test scores.. The absence of Aβ deposition in many patients with chronic neuropsychological impairment after TBI does not support the premise that Aβ pathology progresses over time in the traumatized brain. Early and sequential (11)C-PIB PET examination may clarify the time course of Aβ deposition in the traumatized brain and the relationship between traumatic brain insult and subsequent neuropsychological impairment.

Topics: Adult; Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Brain Injuries; Carbon Radioisotopes; Disease Progression; Female; Humans; Japan; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Prognosis; Thiazoles