Dual PET-fMRI reveals a link between neuroinflammation, amyloid binding and compensatory task-related brain activity in Alzheimer's disease.
Nádia CanárioLília JorgeRicardo MartinsIsabel SantanaMiguel Castelo-BrancoPublished in: Communications biology (2022)
The interplay among neuropathological mechanisms underlying Alzheimer's disease (AD), as neuroinflammation and amyloid-beta (Aβ), as well their impact on neuronal function remains elusive. A major gap in knowledge is the functional impact of neuroinflammation. The posterior cingulate cortex (PCC), as the most prominent site of amyloid pathology in AD, is a pivotal region to investigate the concomitant presence of pathophysiological mechanisms such as microglia activation, indexing neuroinflammation, and changes in task related activity. Here we used a dual PET approach to simultaneously study Aβ load and neuroinflammation (TSPO uptake marker), using 11 C-PiB and 11 C-PK11195 radiotracers, respectively and fMRI to study task related neural activation in an AD sample (n = 19) and matched controls (n = 19). Here we show significantly increased Aβ deposition, neuroinflammation and brain activity related to a visual object working memory task in this key region. Microglia activation was associated with increased brain activity specifically in patients, independently of amyloid binding, raising the possibility that abnormal brain activity might be restored in clinical trials aimed at reducing microglia activation.
Keyphrases
- working memory
- lipopolysaccharide induced
- lps induced
- traumatic brain injury
- inflammatory response
- cerebral ischemia
- functional connectivity
- cognitive impairment
- clinical trial
- resting state
- computed tomography
- pet imaging
- neuropathic pain
- healthcare
- ejection fraction
- cognitive decline
- randomized controlled trial
- pet ct
- attention deficit hyperactivity disorder
- newly diagnosed
- chronic kidney disease
- positron emission tomography
- subarachnoid hemorrhage
- brain injury
- spinal cord injury
- dna binding
- drug induced