Regional analysis of striatal and cortical amyloid deposition in patients with Alzheimer's disease

Abstract

We aimed to analyse the detailed distribution pattern of amyloid-β (Aβ) in the striatum, and to examine whether there is any correlation between Aβ deposition levels in the striatum and cortical regions. Twenty patients with Alzheimer's disease underwent positron emission tomography using (11) C-Pittsburgh Compound B ((11) C-PiB) to quantify the Aβ deposition. Volumes-of-interest analyses were performed on the ventral striatum (VST), pre-commissural dorsal caudate (pre-DCA), post-commissural caudate (post-CA), pre-commissural dorsal putamen (pre-DPU), and post-commissural putamen (post-PU), followed by exploratory voxel-wise analyses. Volumes-of-interest analyses of (11) C-PiB binding showed: VST > pre-DPU (P = 0.004), VST > pre-DCA (P < 0.0001), pre-DPU > post-PU (P < 0.0001), and pre-DCA > post-CA (P < 0.0001), consistent with visual inspection of the (11) C-PiB images. Exploratory voxel-wise analyses of (11) C-PiB binding showed a positive correlation between the VST and the medial part of the orbitofrontal area (P < 0.01 family-wise error corrected). This study confirmed that there were ventral > dorsal, and anterior > posterior gradients of Aβ deposition in patients with Alzheimer's disease, and provided the first evidence of a robust correlation between Aβ deposition levels in the VST and the medial part of the orbitofrontal area. There are well-known anatomical and functional links between these areas. These findings indicated that brain Aβ deposition was not randomly distributed, but had characteristic patterns related to anatomical connectivity and/or functional networks.

Investigating Focal Connectivity Deficits in Alzheimer's Disease Using Directional Brain Networks Derived from Resting-State fMRI

“…The dysregulation of LC-NE neurotransmission likely contributes to behavioral deficits observed in AD. In corroboration, previous literature has pinpointed the same regions (Heneka et al, 2010; Ishibashi et al, 2014) to be affected in AD. Our identification of the LC in the brain stem as the disease focus in AD supports these previous observations and suggests that functional MRI studies of AD, which have been largely cortico-centric (Dennis and Thompson, 2014; Li et al, 2014), must in future investigate the role of this structure in AD.…”

“…Robust correlation has been found between Aβ deposition levels and volume in the orbitofrontal area (Ishibashi et al, 2014). In fact, the amyloid precursor protein (APP) gene contains the sequence for the Aβ peptide, which is concentrated in the senile plaques (SPs) (Cras et al, 1991).…”

Relationship between aging and T1 relaxation time in deep gray matter: A voxel‐based analysis

“…Quantification of T 1 relaxation time has mainly focused on WM and enabled the detection of subtle changes that cannot be detected with conventional MRI . Deep GM structures are also affected in patients with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Parkinson's syndrome . Neurodegenerative diseases often affect older subjects; therefore, our results contribute to the comprehension of normal age‐related changes and the necessity of investigating T 1 relaxation time in pathological states.…”

Relationship of regional brain β-amyloid to gait speed

“…7 Out of all striatal subregions, the dorsal posterior putamen is uniquely interlinked with primary motor, premotor, supplementary motor, and primary somatosensory cortical areas and therefore plays a pivotal role in the modulation of motor circuits. 8,27,28 Supported by evidence that the distribution of Ab in the striatum mirrors the topographic pattern of the functionally distinct corticostriatal circuits, 29 we hypothesized that focal Ab, preferentially in the dorsal posterior putamen, leads to slow gait speed by disrupting motor circuits through its neurotoxic effects. The importance of the dorsal posterior putamen in motor function is further underscored by the clinical observations in a range of neurologic conditions known to affect this brain region selectively (appendix e-5).…”