Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

Abstract

Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18 kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

“…Some failures were due to existing genetic polymorphisms affecting TSPO binding in humans [31][32][33]. While this limitation can be corrected [34][35][36][37], the non-specific role of TSPO in neuroinflammation are more difficult to address [9,38,39], as TSPO is involved in many cellular functions not specific to central inflammation [40][41][42][43][44].…”

Translocator protein in late stage Alzheimer’s disease and Dementia with Lewy bodies brains

“…TSPO density in the human AD and DLB brain has been extensively explored by PET studies using [ 11 C]PK11195, [ 11 C]DAA1106, [ 11 C]vinpocetine, and [ 11 C]PBR28; and by autoradiography studies using [ 3 H]PK11195, [ 3 H] DAA1106, and [ 125 I]DAA1106 . In these studies early stage patients with mild to moderate cognitive impairment (clinical dementia rate (CDR) 1 and 2) were usually recruited and increases in TSPO density were often found in multiple brain regions .…”

In vivo Brainstem Imaging in Alzheimer’s Disease: Potential for Biomarker Development

“…Neuroinflammation in particular is increasingly appreciated for its significant role in the early etiology of AD, and various MRS-detectable metabolites have historically been taken as indicators of neuroinflammatory changes ( Quarantelli, 2015 ). More recently, progress has been made in PET imaging of translocator protein (TSPO) as a biomarker of activated microglia and astrocytes ( Kreisl et al, 2018 ).…”