A recent neuroimaging study published in Communications Biology, a journal within the Nature portfolio, reports a possible link in individuals with Alzheimer disease between neuroinflammation in the brain and task-related activities, independent of amyloid aggregation.1 These early findings may indicate that abnormal brain activity may possibly be restored by targeting neuroinflammation; however, additional studies and clinical trials are still needed to corroborate and build upon these findings.
This study by Canário and colleagues examined the link between brain activity, neuroinflammation caused by microglia, and amyloid aggregation (A𝛃) by using duel positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Two different PET radiotracers were used to simultaneously determine neuroinflammation and A𝛃 accumulation.
PET allows for the in vivo imaging of biomarkers associated with Alzheimer disease (AD). Radiotracers, such as 11C‐labeled Pittsburgh compound B ([11C]PiB), target the amyloid protein associated with AD,2 and have even been used in studies associating amyloid protein to impaired memory.2,3 Similarly, 11C-PK11195 is a PET radiotracer that binds to the translocator protein expressed in activated microglia associated with neuroinflammation.4
Microglia are involved in the CNS immune response, yielding different effects depending on the signals received from the neurons. Typically, homeostatic signals, such as CD200, would elicit an anti-inflammatory response from microglia, but A𝛃 and pathogen-associated molecules cause an inflammatory response.5
Researchers saw a statistically significant (P = 0.013) positive correlation in the posterior cingulate cortex (PCC) between the 11C-PK11195 radiotracer measuring neuroinflammation (microglial activation) and the beta values derived from the fMRI in the AD group whereas no relationship was evident with the control group (P = 0.185). They also did not see a correlation between A𝛃 and fMRI beta values. Higher beta values indicate higher neuronal activation required for the task.1
These results imply that future studies may focus on reducing neuroinflammation to restore abnormal brain activity since neuroinflammation may have an independent role from A𝛃 in cognition in symptomatic AD patients.1
- Canário N, Jorge L, Martins R, Santana I, Castelo-Branco M. Dual PET-fMRI reveals a link between neuroinflammation, amyloid binding and compensatory task-related brain activity in Alzheimer’s disease. Commun Biol. 2022;5(1):1-7. doi:10.1038/s42003-022-03761-7
- Chandra A, Valkimadi P, Pagano G, Cousins O, Dervenoulas G, Politis M. Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer’s disease and mild cognitive impairment. Hum Brain Mapp. 2019;40(18):5424-5442. doi:10.1002/hbm.24782
- Frings L, Spehl TS, Weber WA, Hüll M, Meyer PT. Amyloid-β load predicts medial temporal lobe dysfunction in Alzheimer dementia. J Nucl Med Off Publ Soc Nucl Med. 2013;54(11):1909-1914. doi:10.2967/jnumed.113.120378
- Rissanen E, Tuisku J, Rokka J, et al. In Vivo Detection of Diffuse Inflammation in Secondary Progressive Multiple Sclerosis Using PET Imaging and the Radioligand 11C-PK11195. J Nucl Med Off Publ Soc Nucl Med. 2014;55(6):939-944. doi:10.2967/jnumed.113.131698
- Augusto-Oliveira M, Arrifano GP, Lopes-Araújo A, et al. What do microglia really do in healthy adult brain? Cells. 2019;8(10):1293. doi:10.3390/cells8101293
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