# Positron Emission Tomography in Cerebral Amyloid Angiopathy: A Scoping Review
## 1 Introduction  
Cerebral amyloid angiopathy (CAA) is one of the small vessel diseases (SVDs) [1, 2, 3] with the highest prevalence in the population, and is responsible for multiple consequences, including brain bleeding (convexal subarachnoid hemorrhage and intraparenchymal hemorrhage), cognitive impairment and dementia, and gait disturbances [4]. Its prevalence increases with the age of the population, but the current diagnostic criteria include an age threshold of 50 years, which makes the characteristics of the disease even more significant [5]. CAA is a subtype of SVD that affects the arterioles, capillaries, and leptomeningeal and cortical venules, in which the progressive deposition of non-water-soluble fragments of beta amyloid, in particular, the fragment 1-42, determines the progressive subversion of the structure of the vessel wall, which impacts the vessels' function and structural integrity [4].  
CAA is most frequently associated with the other most prevalent amyloid-related brain disease, namely, Alzheimer's disease (AD) [4]. The co-presence of CAA and AD in the same subject occurs in up to 80% of cases in histopathological series, although this association is reduced if only moderate-severe CAA is considered [4; 6]. The association with AD represents an important element both for the possible overlapping of clinical manifestations and natural history, as well as for diagnostic aspects. In fact, if it is known that a significant proportion of patients with AD have signs of SVD on Magnetic Resonance Imaging (MRI), expressed by both hemorrhagic and non-hemorrhagic markers [7], it is equally true that the diagnosis of AD is made, in accordance with the ATN criteria, on the basis of the demonstration of alteration of beta amyloid (reduced levels in the cerebrospinal fluid--CSF--or cerebral hyperaccumulation in positron emission tomography--PET--with amyloid tracers) and of the tau protein (increased levels in the CSF or tau PET with pathological results) [8]. The coexistence of CAA and AD makes it highly probable that the dosage of neurodegeneration biomarkers in the cerebrospinal fluid and PET with amyloid tracers are altered in patients with CAA, although it is impossible to reliably determine to which of the two diseases the findings can be attributed, vascular or neurodegenerative. In this context, it is also possible to postulate the existence of subgroups of patients with pure CAA and pure AD. Since CAA, in the absence of a previous history of intracerebral hemorrhage (ICH) and clinical manifestations that fall within the current diagnostic criteria (e.g., cognitive impairment and transient focal neurological episodes), can be diagnosed with a sensitivity and specificity of approximately 60%, the availability of diagnostic support with techniques other than MRI could be useful [5]. The number of studies that have explored the role of PET with amyloid tracers in CAA is few, and the number of patients is also limited; furthermore, in these studies, there is no contemporary assessment of CSF biomarkers that can help to define the co-presence of more than one neurodegenerative disease [9]. Despite these limitations, the approach appears promising, particularly in patients with lobar ICH, in which the histopathology is consistent with a diagnosis of underlying CAA in only 50% of cases [6]; and in patients with inflammatory manifestations, such as CAA-related inflammation, which are very similar to the amyloid-related imaging abnormalities described, to a lesser extent, as spontaneous events, and to a greater extent, as iatrogenic events in AD patients treated with immunotherapy [10; 11; 12; 13; 14; 15].  
The aim of this scoping review is to assess the role and the potential application of PET with amyloid tracers in CAA patients, highlighting the strengths and limitations of the available studies and identifying future perspectives.