Christian BT, Wooten DW, Hillmer AT, Tudorascu D, Murali D, Barnhart TE, Harding S, Asthana S, Sager MA, Johnson SC.
The relation of serotonin 5-HT1A receptors and amyloid load in prodromal AD.
Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;
Objective: The goal of this study is to identify a neural system that reveals a measurable response prior to the
development of AD. The serotonin (5-HT1A) system was examined under conditions of increasing amyloid burden
in prodromal AD subjects.
Methods: A total of 15 subjects have undergone multimodality imaging and neuropsychological testing (RAVLT
and CDR), consisting of 11 controls, with 4 of the subjects classified as gdeclinersh based upon repeated RAVLT
tests, and 4 with amnestic MCI. Dynamic PET scans using [C-11]PIB (amyloid binding) and [C-11]WAY100635
(5-HT1A receptor binding) and T1- and T2- weighted MRI scans were acquired. Parametric images of specific
binding (DVR) were created from the PET data and spatially transformed into normalized space for ROI and voxelbased
analysis. Partial volume correction was used for the ROI based data and mean cortical values were used
as an index for PIB binding.
Results: A positive correlation was found between PIB binding and 5-HT1A binding in the hippocampus (Hi)
(R = 0.72, p = 0.003) and the posterior cingulate gyrus (PCG) (R = 0.63, p = 0.015). There was a significant difference
in median values between CDR_SOB = 0 and CDR_SOB>0 for PIB binding, 5-HT1A Hi and PCG (p = 0.004, 0.039,
0.005, respectively). Voxel-based analyses revealed a negative correlation between the global PIB and 5-HT1A
binding in the raphe nuclei (p = 0.005, uncorrected).
Conclusion: These data suggest there is an upregulation of 5-HT1A cortical postsynaptic receptors with increasing
amyloid burden and a downregulation of 5-HT1A binding to the autoreceptors of the raphe nuclei. The serotonin
5-HT1A system may provide an early indication of neural changes prior to the onset of AD.