Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment
Year: 2021
Type: article
Abstract: BACKGROUND: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined. OBJECTIVE: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). METHODS: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. RESULTS: Multiple regression analyses controlling for age, education, and APOE ɛ4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for Aβ42 (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of Aβ42 (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (p s < 0.05). CONCLUSION: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-201382
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Veterans Affairs, Alzheimer's Association, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: G1012222616, G1032285814, G104586243, G1174407038, G1298807586, Cerebral Arterial Compliance and Cognitive Function in MCI, G1554142629, G1593117279, G1650819308, G1775224375, G1880935189, G2100670906, G2105457377, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2484314121, G2522063444, Cognitive Process Scores to Improve Preclinical AD Detection, G279072258, G2835601961, G2957681590, G29951154, G3146424788, G3216574877, G363319880, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G43180419, G4501223628, G4800177743, New Quantitative Neuroimaging Metrics of Structural and Functional Connectivity of the Locus Coeruleus as a Novel Biomarker of Alzheimer's Disease Pathogenesis and Progression, G5062101045, G5207404921, G5209990037, G528601746, G5363700876, G5365730499, G5654639750, G5678256514, Alzheimer's Disease Neuroimaging Initiative, G5740349702, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G665855531, G6719828067, G684805955, G6899163935, G6948409098, G72415811, G7298697282, G764699806, Intracranial arterial compliance, cerebral blood flow, and dementia risk in older adults with type 2 diabetes, G7799614282, G781725486, G8228018387, G8281378126, G839208290, G8852128998, G8895907669, G8897063270, G8957659042, G9000009473, G9000027605, G9000039018, G9000122335, Alzheimer's Disease Neuroimaging Initiative (ADNI4)
OpenAlex ID: W3135440279