MR Microscopy of Human Amyloid-β Deposits: Characterization of Parenchymal Amyloid, Diffuse Plaques, and Vascular Amyloid

Abstract

Cerebral deposits of amyloid-β peptides (Aβ) form the neuropathological hallmarks of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In the brain, Aβ can aggregate as insoluble fibrils present in amyloid plaques and vascular amyloid, or as diffuse plaques consisting of mainly non-fibrillar Aβ. Previously, magnetic resonance imaging (MRI) has been shown to be capable of detecting individual amyloid plaques, not only via the associated iron, but also Aβ itself has been suggested to be responsible for a decrease in the image intensity. In this current study we aim to investigate the MRI properties of the different cerebral Aβ deposits including diffuse plaques and vascular amyloid. Postmortem 60-μm-thick brain sections of AD, CAA, and Down's syndrome patients, known to contain Aβ, were studied. High resolution T2*- and T2-weighted MRI scans and quantitative relaxation maps were acquired using a microcoil on a Bruker 9.4T MRI system. Specific MRI characteristics of each type of Aβ deposit were examined by co-registration of the MRI with Congo Red and Aβ-immunostainings of the same sections. Our results show that only fibrillar Aβ, present in both vascular and parenchymal amyloid, induced a significant change in T2* and T2 values. However, signal changes were not as consistent for all of the vessels affected by CAA, irrespective of possible dyshoric changes. In contrast, the non-fibrillar diffuse plaques did not create any detectable MRI signal changes. These findings are relevant for the interpretation and further development of (quantitative) MRI methods for the detection and follow-up of AD and CAA.

Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer’s disease brains

“…Because this hydrophobicity is related to the concentration of the amyloid peptide, diffuse deposits are probably less prone to be revealed by Gd-stained MRI than compact plaques. Interestingly, previous studies have shown that diffuse deposits are not detected by MRI without contrast agents in mice 42 or in human brains 43 . Thus, it seems that Gd-stained MRI does not improve the ability to detect diffuse plaques as compared to contrast-agent free MRI.…”

Quantification of β-Amyloidosis and rCBF with Dedicated PET, 7 T MR Imaging, and High-Resolution Microscopic MR Imaging at 16.4 T in APP23 Mice

“…Wengenack et al reported that the fast decay of transverse magnetization (T 2 *) is not solely attributed to the presence of iron within the amyloid plaques in the cortex and hippocampus in APPPS1 double transgenic mice (27). This notion was further supported by Nabuurs et al, as only fibrillar amyloid plaques rather than diffuse plaques induced significant changes in either T 2 or T 2 * values and the loss of transverse magnetization was not necessarily correlated with the presence of iron within amyloid deposits (28). We now provide further evidence that the density of the amyloid deposition is a key factor for fast transverse magnetization decay, as T 2 * signal intensity is inversely correlated with amyloid deposition density within single amyloid plaques.…”

Quantitative comparison of different iron forms in the temporal cortex of Alzheimer patients and control subjects

“…An increase may also originate from susceptibility changes occurring in tissue lesions, i.e. A β and τ -tangles 83 , as pointed out by the trend between and Braak Stage shown in Fig. 2 , or be caused by microhemorrhages, or myelin changes 36 , 38 also taking place in AD 25 .…”