Down syndrome, beta-amyloid and neuroimaging

Abstract

This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we have learned a great deal about Aβ in DS in terms of characterizing age of onset of this pathology and it is exciting to note that there is a clinical trial in DS targeting Aβ that may lead to clinical benefits.

Metabolic and Vascular Imaging Biomarkers in Down Syndrome Provide Unique Insights Into Brain Aging and Alzheimer Disease Pathogenesis

“…Panel (E) shows examples of amyloid PiB-PET imaging (top) and FDG-PET imaging (bottom). Images from (A–D) were modified from Figure 5 with permission of Elsevier Press (Head et al, 2018 ). Images from (E) were modified from Figure 1 reproduced with permission from Dr. M. Rafii and under the Creative Commons Attribution License (CC BY) (Rafii et al, 2015 ).…”

Neuropathological correlates of amyloid PET imaging in Down syndrome

“…In DS subjects aged >40 years, levels of cortical Aβ deposition are similar to those observed in sporadic, late onset AD (Davidson, Robinson, Prasher, & Mann, ; Head, Lott, Wilcock, & Lemere, ; Lemere et al, ; Liu et al, ; Mann, ; Mann & Esiri, ; Wisniewski, Bancher, Barcikowska, Wen, & Currie, ) and in addition to diffuse plaques involve cored plaques associated with dystrophic neurites (neuritic plaques), which are of neuropathological diagnostic significance in AD. Understanding structural properties, biochemical constituents, and evolution of morphologically diverse Aβ plaques and other AD‐related pathology within and between brain regions in relation to age and development of dementia is needed to guide interpretation of amyloid PET imaging of subjects with DS (Head, Helman, Powell, & Schmitt, ; Neale, Padilla, Fonseca, Holland, & Zaman, ). Compared to the extensive number of amyloid PET studies performed in AD (Cohen et al, ), there are relatively few amyloid PET studies of DS (Annus et al, , ; Cohen et al, ; Cole et al, ; Handen et al, ; Hartley et al, ; Jennings et al, ; Landt et al, ; Lao et al, , ; Mak et al, ; Matthews et al, ; Rafii et al, ; Sabbagh et al, ), even fewer longitudinal studies (Hartley et al, ; Lao et al, ; Tudorascu et al, ), and only one imaging‐to‐autopsy analysis (Sabbagh et al, ).…”

Amyloid β oligomers inhibit growth of human cancer cells

“…It is known that β-amyloids affect cells, especially neurons, and can cause various diseases [42–44]. The effects are different, while the structural peculiarities of the species which were used for testing remained mainly unexplored.…”