Elevated Inflammatory Markers and Arterial Stiffening Exacerbate Tau but Not Amyloid Pathology in Older Adults with Mild Cognitive Impairment.
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.
['Clark|Alexandra L|AL|', 'Weigand|Alexandra J|AJ|', 'Thomas|Kelsey R|KR|', 'Solders|Seraphina K|SK|', 'Delano-Wood|Lisa|L|', 'Bondi|Mark W|MW|', 'Bernier|Rachel A|RA|', 'Sundermann|Erin E|EE|', 'Banks|Sarah J|SJ|', 'Bangen|Katherine J|KJ|', '|||']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D015415:Biomarkers D016022:Case-Control Studies D060825:Cognitive Dysfunction D003937:Diagnosis, Differential D006801:Humans D007249:Inflammation D008297:Male D008875:Middle Aged D009483:Neuropsychological Tests D010446:Peptide Fragments D010766:Phosphorylation D012044:Regression Analysis D016875:tau Proteins
tau mild cognitive impairment inflammation Cerebrospinal fluid vascular dysfunction