Cholecystokinin and Alzheimer's disease: a biomarker of metabolic function, neural integrity, and cognitive performance.

Cholecystokinin (CCK) is a satiety hormone that is highly expressed in brain regions like the hippocampus. CCK is integral for maintaining or enhancing memory and thus may be a useful marker of cognitive and neural integrity in participants with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD). Cerebrospinal fluid (CSF) CCK levels were examined in 287 subjects from the Alzheimer's Disease Neuroimaging Initiative. Linear or voxelwise regression was used to examine associations between CCK, regional gray matter, CSF AD biomarkers, and cognitive outcomes. Briefly, higher CCK was related to a decreased likelihood of having mild cognitive impairment or AD, better global and memory scores, and more gray matter volume primarily spanning posterior cingulate cortex, parahippocampal gyrus, and medial prefrontal cortex. CSF CCK was also strongly related to higher CSF total tau (R2 = 0.342) and p-tau-181 (R2 = 0.256) but not Aβ1-42. Tau levels partially mediated CCK and cognition associations. In conclusion, CCK levels may reflect compensatory protection as AD pathology progresses.