Pittsburgh Compound B

Radiation-induced brain injury (RIBI) and Alzheimer's disease (AD) share key pathological features, including β-amyloid (Aβ) plaque formation and microtubule (MT) destabilization, both contributing to neurodegeneration. This pilot study assessed Aβ deposition and MT stability in non-human primates (NHPs) exposed to ionizing radiation, utilizing [¹¹C]PiB and [¹¹C]MPC-6827 PET imaging to explore neurodegenerative mechanisms. Fourteen rhesus macaques, seven irradiated and seven controls underwent PET imaging. Tracers were synthesized and brain regions (ex. cingulate, hippocampus, and occipital lobe) were analyzed for tracer uptake. Although no statistically significant whole-brain differences in tracer uptake were found between irradiated and control groups, significant regional differences were observed in the occipital lobe, where irradiated NHPs exhibited higher [¹¹C]MPC-6827 uptake (p < 0.0001), suggesting MT destabilization. No significant differences were found in [¹¹C]PiB uptake. Correlation analysis revealed a slight positive association (Pearson r = 0.2866) between irradiation dose and [¹¹C]MPC-6827 uptake. These findings suggest that irradiation-induced MT destabilization may be region-specific, offering insights into shared neurodegenerative pathways in RIBI and AD, highlighting the potential of [¹¹C]MPC-6827 as a marker for early neuronal dysfunction in irradiated brains.

The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid‐positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid‐β.

Linear mixed‐effects modeling investigated overall and sex‐specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to the estimated age of amyloid onset in a cohort of 78 amyloid‐positive Baltimore Longitudinal Study of Aging (BLSA) participants (n = 45 male; follow‐up time: 6.8 years [SD 3.31]). Amyloid status was ascertained with 11C‐Pittsburgh compound B (PiB) PET imaging.

After amyloid onset, men displayed steeper increases in pTau181, pTau231, and neurofilament light (NfL) compared to women. In this same period, men demonstrated steeper declines in brain volume and cognitive performance.

These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become amyloid‐positive.

Steeper rates of increase in pTau and GFAP among amyloid‐positive individuals.After amyloid onset, steeper increases in pTau and NfL concentrations in men than in women.Steeper declines in brain volume and cognition in men corroborate biomarker results.