β-Amyloid Distributions in Neurodegenerative Disorders through PET CT Imaging

Introduction: Amyloid PET CT plays a pivotal role in diagnosing Alzheimer’s Disease (AD) through noninvasive detection of amyloid plaques, a hallmark of AD pathology. However, AD's clinical presentation often overlaps with other neurodegenerative disorders such as Cerebral Amyloid Angiopathy (CAA), Frontotemporal Dementia (FTD), and Lewy Body Dementia (LBD). As radiologists, discerning these distinct distribution patterns can help in accurate diagnosis. This poster aims to elucidate and compare the amyloid PET CT tracer uptake distributions across AD, CAA, FTD, and LBD.

Alzheimer’s Disease is marked by the accumulation of Amyloid β (Aβ) and Tau protein neurofibrillary tangles, leading to neuroinflammation, neuronal loss, and death. Symptoms of AD often resemble those in CAA, FTD, and LBD, some also with Aβ amyloid accumulation as part of disease progression. Currently, amyloid PET CT is used in uncertain cases of suspected AD, with evidence of cognitive impairment. Analysis of Amyloid PET distributions among these neurodegenerative diseases may reveal diagnostic benefits, especially when combined with clinical information. ¹¹C-labeled Pittsburgh compound B (C-PiB), an amyloid PET tracer, has been used in research due to its capacity to bind aggregated Aβ with high sensitivity and specificity as well as vascular amyloid in CAA. Other Amyloid PET tracers, including ¹⁸F-based tracers, show differential binding patterns in different neurodegenerative disorders.

Methods: Through our exhibit, we will provide background information on AD, CAA, FTD, and LBD. We then review quantitative methodology of amyloid PET CT imaging, including the standardized uptake value ratio (SUVr) for determining amyloid burden. We explore the amyloid PET imaging findings and distributions between these conditions. We include the discussion of how CAA and AD are differentiated in a flow chart. We then discuss how amyloid PET CT can be used for diagnostic purposes, possibly with the addition of other clinical information.

Results: In Alzheimer’s disease, amyloid PET CT showed generalized uptake throughout the cortex with intensity depending on severity of the disease. But it is possible for the uptake in AD to be concentrated in the neocortex and striatum while sparing the medial temporal lobes and primary unimodal cortices. In contrast, FTD shows limited uptake of amyloid, effectively ruling out AD.There are some key clinical signifiers on presentation that can help to point toward AD versus other presentations. AD rarely presents before the age of 65; this can help distinguish against FTD, which has a mean age of onset of 53. Depending on the variant of FTD, the patient will present with more signs of executive dysfunction, such as disinhibition, apathy, hyperorality, and a greater comparative decline in social cognition. When comparing between CAA and AD, CAA shows lower global uptake with greater uptake in occipital regions, whereas AD shows higher global uptake with greater uptake in the temporal lobes. CAA may also present with dementia, but with increased risk of lobar hemorrhage due to deposition of amyloid in blood vessel walls. Amyloid PET CT is not useful in differentiating AD from LBD due to overlapping binding patterns despite some difference in overall uptake. However, distinguishing features present in LBD include parkinsonism, visual hallucination, and REM sleep behavior disorder.

Conclusions: Amyloid PET CT is valuable for diagnosing AD amidst clinical uncertainty, showcasing unique amyloid distributions in AD, CAA, FTD, and LBD. Its specificity remains limited in differentiating these conditions. Developing diagnostic criteria that incorporate amyloid PET CT could significantly enhance differentiation of these diseases when used alongside clinical presentation. With early results of significant reduction in Amyloid PET after treatment with anti-Aβ monoclonal antibodies, PET CT can be an emerging tool for clinical monitoring of disease progression and treatment response.