The Role of Amyloid PET in Imaging Neurodegenerative Disorders: A Review

Abstract

Imaging of amyloid deposition using PET has been available in research studies for 2 decades and has been approved for clinical use by the U.S. Food and Drug Administration, the European Medicines Agency, and other regulatory agencies around the world. Amyloid PET is a crucial tool for the diagnosis of Alzheimer disease, as it allows the noninvasive detection of amyloid plaques, a core neuropathologic feature that defines the disease. The clinical use of amyloid PET is expected to increase with recent accelerated approval in the United States of aducanumab, an antiamyloid monoclonal antibody, for the treatment of mild cognitive impairment and mild dementia due to Alzheimer disease. However, amyloid pathology can also be found in cognitively unimpaired older adults and in patients with other neurodegenerative disorders. The aim of this review is to provide an up-to-date overview of the application of amyloid PET in neurodegenerative diseases. We provide an in-depth analysis of the clinical, pathologic, and imaging correlates; a comparison with other available biomarkers; and a review of the application of amyloid PET in clinical trials and clinical utility studies.

Keywords: Alzheimer disease; PET; PET/MRI; amyloid PET; neurodegenerative diseases; neurology.

Graphical abstract

FIGURE 1.

Postmortem measures of amyloid pathology. (A) Types of amyloid deposits. (B) Amyloid angiopathy. (C) Distribution of diffuse and neuritic plaques. (D) Neuritic plaque density (highest density score observed in brain). (A, B, and D are from UCSF Neurodegenerative Disease Brain Bank; C is reprinted with permission of (53).) NP = neuritic plaques.

FIGURE 2.

Structures of thioflavin-T, ¹¹C-PiB, ¹⁸F-flutafuranol, and Food and Drug Administration–approved Aβ PET tracers. (Reprinted from (54).)

FIGURE 3.

Examples of negative and positive Aβ PET findings using different tracers. (¹⁸F-flutafuranol images are courtesy of Victor Villemagne and Christopher C. Rowe.)

FIGURE 4.

Evolution of amyloid PET positivity across AD spectrum. (A) Positive ¹¹C-PiB scan of cognitively normal (CN) participant, in which significant binding is observed in precuneus, posterior cingulate cortex, and medial prefrontal areas. (B) Positive ¹¹C-PiB scan of MCI patient, in which significant and moderate binding is observed throughout cortex. (C) Positive ¹¹C-PiB scan of AD patient, in which significant and severe binding is observed throughout cortex.