Neuroinflammation in Neurodegenerative Diseases: A Narrative Update (2020–2026) on Metabolic, Molecular, Morphological, and Functional Imaging

Abstract

Neuroinflammation is increasingly recognized as a biologically relevant component of neurodegenerative disease, yet its in vivo imaging remains difficult to interpret. This narrative update synthesizes original imaging studies published between January 1, 2020, and May 17, 2026, and examines how positron emission tomography (PET), magnetic resonance imaging (MRI), and hybrid or multimodal approaches characterize glial and neurovascular processes. The most extensive human evidence is available for Alzheimer’s disease, in which translocator protein (TSPO) PET has been associated with tau burden, amyloid-β deposition, Braak-like propagation, cognitive decline, network dysfunction, and genotype-dependent disease biology. In frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, Parkinson’s disease, and multiple system atrophy, evidence is more limited and heterogeneous; nevertheless, selected studies support mechanistic phenotyping, prognostic enrichment, and, in multiple system atrophy, formal differential-diagnostic testing. Emerging targets include monoamine oxidase-B, colony-stimulating factor 1 receptor, P2X7 receptor, and acetate metabolism, whereas fluorodeoxyglucose (FDG) PET, diffusion MRI, quantitative susceptibility mapping, and blood-brain barrier imaging provide complementary metabolic, microstructural, and neurovascular information. Neuroinflammation imaging should therefore be interpreted as a collection of target-specific, stage-dependent biological readouts rather than as a unitary measure of inflammation. Because most studies report associations, colocalization, or prognostic models rather than diagnostic accuracy, sensitivity and specificity are discussed only when explicitly evaluated in the original study. Current evidence supports neuroinflammation imaging primarily for mechanistic investigation, patient stratification, and trial enrichment rather than routine clinical deployment.