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

• Published in: Neurobiology of aging 2019-04, Vol.76, p.201-207
• Main Authors: Plagman, Alexandra, Hoscheidt, Siobhan, McLimans, Kelsey E., Klinedinst, Brandon, Pappas, Colleen, Anantharam, Vellareddy, Kanthasamy, Anumantha, Willette, Auriel A.
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers; Biomarkers - cerebrospinal fluid; Brain - diagnostic imaging; Brain - pathology; Cholecystokinin; Cholecystokinin - cerebrospinal fluid; Cognition; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; MRI; Neuroimaging; Neuropathology; Severity of Illness Index; tau Proteins - cerebrospinal fluid
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.01.002

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. •Higher CCK predicted better cognitive outcomes.•Higher CCK predicted more GM in memory-specific regions of the brain.•Higher CCK is related to more CSF tau and p-tau.•Total tau reduced the influence of CCK on memory factor by nearly half.