Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease

Abstract

As the societal and economic burdens of Alzheimer's disease (AD) continue to mount, so does the need for therapies that slow the progression of the illness. Beta amyloid has long been recognized as the pathologic hallmark of AD, and the past decade has seen significant progress in the development of various immunotherapeutic approaches targeting beta amyloid. This paper reviews active and passive approaches aimed at beta amyloid, with a focus on clinical trial data.

Figure 1

Passive and active immunotherapeutic approaches to beta-amyloid clearance. Beta-amyloid immunotherapeutic compounds currently in clinical trials utilize anti-beta-amyloid antibodies, generated through either passive or active immunotherapy approaches (left), to target beta amyloid and promote its clearance from the brain and proteolysis (right), potentially reversing the neuropathology that leads to cognitive dysfunction. Aβ: beta amyloid.

Figure 2

Positron emission tomography (PET) carbon-11-labelled Pittsburgh compound B (¹¹C-PiB) images from patients treated with bapineuzumab and those given placebo [57]. Reprinted from [57] with permission from Elsevier. Changes from screening to week 78 in patients treated with bapineuzumab (a, b) and in patients treated with placebo (c, d). Mean ¹¹C-PiB PET changes are shown at the top center of each panel for each patient. The scale bar shows the PiB uptake ratios relative to cerebellum by color. The scans before and after treatment are from MRI coregistered images in the same plane.