Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

[zingo]

Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

Importance The association between peripheral inflammatory biomarkers and Alzheimer disease (AD) is not consistent in the literature. It is possible that chronic inflammation, rather than 1 episode of inflammation, interacts with genetic vulnerability to increase the risk for AD.

Objective To study the interaction between the apolipoprotein E (ApoE) genotype and chronic low-grade inflammation and its association with the incidence of AD.

Design, Setting, and Participants In this cohort study, data from 2656 members of the Framingham Heart Study offspring cohort (Generation 2; August 13, 1971-November 27, 2017) were evaluated, including longitudinal measures of serum C-reactive protein (CRP), diagnoses of incident dementia including AD, and brain volume. Chronic low-grade inflammation was defined as having CRP at a high cutoff level at a minimum of 2 time points. Statistical analysis was performed from December 1, 1979, to December 31, 2015.

Main Outcomes and Measures Development of AD and brain volumes.

Results Of the 3130 eligible participants, 2656 (84.9%; 1227 men and 1429 women; mean [SD] age at last CRP measurement, 61.6 [9.5] years) with both ApoE status and longitudinal CRP measurements were included in this study analysis. Median (interquartile range) CRP levels increased with mean (SD) age (43.3 [9.6] years, 0.95 mg/L [0.40-2.35 mg/L] vs 59.1 [9.6] years, 2.04 mg/L [0.93-4.75 mg/L] vs 61.6 [9.5] years, 2.21 mg/L [1.05-5.12 mg/L]; P < .001), but less so among those with ApoE4 alleles, followed by ApoE3 then ApoE2 genotypes. During the 17 years of follow-up, 194 individuals (7.3%) developed dementia, 152 (78.4%) of whom had AD. ApoE4 coupled with chronic low-grade inflammation, defined as a CRP level of 8 mg/L or higher, was associated with an increased risk of AD, especially in the absence of cardiovascular diseases (hazard ratio, 6.63; 95% CI, 1.80-24.50; P = .005), as well as an increased risk of earlier disease onset compared with ApoE4 carriers without chronic inflammation (hazard ratio, 3.52; 95% CI, 1.27-9.75; P = .009). This phenomenon was not observed among ApoE3 and ApoE2 carriers with chronic low-grade inflammation. Finally, a subset of 1761 individuals (66.3%) underwent brain magnetic resonance imaging, and the interaction between ApoE4 and chronic low-grade inflammation was associated with brain atrophy in the temporal lobe (β = –0.88, SE = 0.22; P < .001) and hippocampus (β = –0.04, SE = 0.01; P = .005), after adjusting for confounders.

Conclusions and Relevance In this study, peripheral chronic low-grade inflammation in participants with ApoE4 was associated with shortened latency for onset of AD. Rigorously treating chronic systemic inflammation based on genetic risk could be effective for the prevention and intervention of AD.

https://jamanetwork.com/journals/jamane ... le/2707427

[Julie G]

Thank you, zingo. This is clearly very important for us. In The End of Alzheimer's, Dr. Bredesen recommends a high sensitivity CRP <0.9mg/L. I think most in our community have already gotten this message...

[circular]

Thank you, zingo. This is clearly very important for us. In The End of Alzheimer's, Dr. Bredesen recommends a high sensitivity CRP <0.9mg/L. I think most in our community have already gotten this message...

I have the message, now if I could just get mine down! It's time to test it again and see if it's still high

[circular]

Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

zingo thanks for posting this. A couple doctors haven't taken my high hsCRP too seriously, I think mainly because they really don't know what to recommend. I think I will take this paper in and request a coronary calcium scan through insurance, since I read that high hsCRP can relate to coronary plaque too, and I have a trail of high scores. If deeper ketosis doesn't help reduce my hsCRP, then I may have to re-introduce some grain fiber while trialing the Mind/Mediterranean-DASH diet and see if that does:

Adherence to the Mediterranean Diet and Inflammatory Markers.

[dcox]

Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

Welcome zingo!

Thank you for the link to this new study associating chronic inflammation with AD risk in ApoE4 carriers. It's always great to stay on top of the latest studies as we go forward. Here is a link to the section in our Wiki about Inflammation and LPS (lipopolysaccharides) if you are interested in more information on this topic. You can also use the spyglass icon in the upper right of any page to search what has been discussed previously about a topic you are interested in.

We would love to here your story and what has brought you to ApoE4.info, feel free to post on the Our Stories forum anytime.

As you explore the site you will find it has an amazing amount of information from people from all over the world who are preventing, reversing, and stopping AD in its tracks. Here you will find support, encouragement, and hope from people who are very passionate about their own journeys and the journeys of others.

If you are looking for a place to begin I recommend the Primer, written by Stavia one of our most active members a Doctor, and E4/E4 herself, this is an amazing place to start, or continue learning, as she truly put her heart into writing it.

Again, welcome! We look forward to learning more about your journey as you share more and learn with us.

Find your joy and hope in each new day and each new discovery along your path,
Deb