The relation between neuroinflammation, amyloid-β load, grey matter loss and brain activity in visual object recognition regions in Alzheimer's Disease

The regional impact of amyloid-β (Aβ) load and neuroinflammation on brain integrity and function is essential to understand the pathophysiology of Alzheimer's disease (AD), yet it is still lacking in the current literature, particularly in regions involved in visual object recognition. Here, using a multimodal approach, we investigated AD-related neuropathological changes and their impact on task-related responses in core visual object recognition areas of the ventral stream: FFA, FBA, LOCv, PPA and VWFA. We combined 11C-PK11195 PET measures of neuroinflammation, 11C-PIB PET measures of Aβ load, MRI structural measures of grey matter and functional MRI (fMRI) BOLD response, using a visual recognition task, in 20 AD patients and 17 Aβ negative healthy controls. Mixed repeated-measure ANOVAS were computed to assess which regions differed between groups for each data modality, and partial correlation tests were used to explore associations across modalities. We found in mild AD patients higher levels of atrophy and Aβ, as compared to relatively preserved visual activation and neuroinflammation levels. An association between Aβ levels and neuronal response was found in right LOCv, possibly suggesting an early transient subclinical impact of Aβ on brain function. We also found an interesting pattern of hemispheric asymmetry, with concurrent atrophy and Aβ load in the left hemisphere. Overall, these findings suggest differential vulnerability to pathological processes along the visual ventral stream in AD, characterized by relatively preserved functional response and neuroinflammatory status, alongside increased leftward susceptibility to GM atrophy and Aβ deposition.