Multimodal PET Imaging of Amyloid and Tau Pathology in Alzheimer Disease and Non–Alzheimer Disease Dementias

Positron Emission Tomography (PET) and Neuroimaging in the Personalized Approach to Neurodegenerative Causes of Dementia

“…Concerning in vivo tau imaging’s role in AD, the non-invasive assessment of the spatial and temporal pattern of tau deposition over time may provide an insight into the role tau plays in AD and may lead to establishing the relation between cognition, genotype, neurodegeneration, and other biomarkers in AD. The topographic distribution of tau tracers ( 18 F-AV-1451, 18 F-THK535149, and 11 C-PBB3) in amnesic MCI or AD dementia, compared with normal aging, is consistent with Braak staging, with more prominent tracer binding in inferior and lateral temporoparietal cortices, parieto-occipital cortices, posterior cingulate cortices, and the precuneus and less prominent in frontal regions and primary sensorimotor cortices [ 41 , 42 , 43 ]. Moreover, it is essential to underline the relationship between tau spreading and disease progression [ 44 ]: therefore, once validated in clinical practice, selective tau imaging might be useful as a diagnostic, prognostic, and progression biomarker and as a surrogate marker for the monitoring of efficacy and patient recruitment for anti-tau therapeutic trials [ 45 ].…”

“…Functional neuroimaging with FDG-PET is used to confirm the clinical hypothesis regarding the localization of neurological changes, which may lead to the differential diagnosis of FTD with AD, DLB, or pathologies most often underlying the condition [ 41 ]. The diagnosis of FTD may be a challenge, especially in the prodromal stage, where behavioral changes may mimic psychiatric disorders and cognitive impairment is absent or may present as mild behavioral impairment.…”

“…Amyloid PET imaging usually displays no tracer retention in patients with the clinical syndrome of FTD [ 51 , 52 ] ( Figure 3 ); therefore, it can be used in the differential diagnosis in order to exclude AD when the suspected underlying pathology is FTD, especially in cases clinically manifesting as behavioral variant FTD (bvFTD) or PPA (Primary Progressive Aphasia). In fact, in the case of a patient that presents clinical features of FTD and a positive amyloid imaging, the diagnosis may be AD or mixed pathologies (coexisting FTD and AD that both contribute to dementia), or the positive scan may be interpreted as an incidental finding (therefore relatively low neurofibrillary alteration that is not contributory to symptoms) [ 41 ]. The use of amyloid PET imaging is considered most appropriate when patients present with cognitive impairment that could be attributed to AD.…”

“…The use of amyloid PET imaging is considered most appropriate when patients present with cognitive impairment that could be attributed to AD. Nevertheless, where the clinician is uncertain, the confirmation of presence or absence of amyloid may influence the diagnosis [ 41 , 53 , 54 , 55 ].…”

“…In the past few years, several studies have demonstrated the potential uses of an imaging biomarker that evaluates in vivo tau retention, which represents a promising, useful biomarker not only for AD but also for other forms of dementia that presents tauopathies, including FTD [ 41 ]. In vivo tau PET imaging presents opportunities to improve both clinical practice and research for the spectrum of FTD, including primary tauopathies as well as TDP-43 proteinopathies.…”