From clinical phenotype to proteinopathy: molecular neuroimaging in neurodegenerative dementias

• Published in: Arquivos de neuro-psiquiatria 2022-05, Vol.80 (S 05), p.24-35
• Main Authors: Studart-Neto, Adalberto, Coutinho, Artur Martins
• Format: Article
• Language: English
• Subjects: Affinity; Alzheimer Disease; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid; Amyloid beta-Peptides; Anatomy; Biomarkers; Brain architecture; Dementia; Dementia disorders; Differential diagnosis; Fluorodeoxyglucose F18; Frontotemporal dementia; Glucose metabolism; Humans; Information processing; Lewy bodies; Ligands; Medical imaging; Neurodegenerative diseases; Neuroimaging; NEUROLOGY OF COGNITIVE AND BEHAVIORAL DISORDERS; NEUROSCIENCES; Phenotype; Phenotypes; Positron emission tomography; Positron-Emission Tomography - methods; Protein folding; Proteins; PSYCHIATRY; Tau protein; tau Proteins; tau Proteins - metabolism; β-Amyloid
• ISSN: 0004-282X; 1678-4227; 1678-4227
• DOI: 10.1590/0004-282X-ANP-2022-S138

ABSTRACT Neurodegenerative dementias are characterized by the abnormal accumulation of misfolded proteins. However, its diagnostic criteria are still based on the clinical phenotype. The development of biomarkers allowed in vivo detection of pathophysiological processes. This article aims to make a non-systematic review of the use of molecular neuroimaging as a biomarker. Molecular neuroimaging is based on the use of radiotracers for image acquisition. The radiotracer most used in PET is 18 F-fluorodeoxyglucose (FDG), with which it is possible to study the regional brain glucose metabolism. The pattern of regional hypometabolism provides neuroanatomical information on the neurodegenerative process, which, in turn, has a good specificity for each type of proteinopathy. FDG is very useful in the differential diagnosis of neurodegenerative dementias through the regional pattern of involvement, including dementia with Lewy bodies and the spectrum of frontotemporal dementia. More recently, radiotracers with specific ligands to some of the pathological proteins have been developed. Pittsburgh compound B (PIB) labeled with 11 C and the ligands that use 18 F (florbetapir, florbetaben and flutemetamol) are the most used radiotracers for the detection of insoluble β-amyloid peptide in Alzheimer's disease (AD). A first generation of ligands for tau protein has been developed, but it has some affinity for other non-tau protein aggregates. A second generation has the advantage of having a higher affinity for hyperphosphorylated tau protein, including in primary tauopathies.