TUESDAY, March 19, 2013 (MedPage Today) — Genetics and high blood pressure appear to interact to increase deposits in the brain of a protein involved in the pathology of Alzheimer's disease, researchers reported.


But people with just one of those factors were not significantly different in terms of beta-amyloid deposition in the brain from volunteers with neither, Rodrigue and colleagues reported online in JAMA Neurology.

And within the group with the genetic risk factor, unmedicated hypertension was associated with the greatest risk for accumulating beta-amyloid, while participants with controlled hypertension had significantly less amyloid burden than the unmedicated group and just slightly more than those without hypertension.

Since hypertension is highly responsive to treatment, the researchers argued, medication or lifestyle modifications "may be able to prevent, or at least slow, pathological aging."

Current theories suggest that deposition of beta-amyloid in the brain is one of the earliest signs of Alzheimer's, Rodrigue and colleagues noted, and determining what factors affect that process might help with early detection and treatment.

The E4 allele of the apolipoprotein E (ApoE) gene is associated with increased risk for Alzheimer's – up to 12-fold higher for people with two copies of the variant, compared with those with two copies of the E3 allele, Rodrigue and colleagues noted.

As well, epidemiological studies have linked vascular disease with an increased risk for Alzheimer's, so the researchers hypothesized that hypertension and the ApoE4 allele might have a synergistic effect on beta-amyloid deposition.

To find out, they studied 147 cognitively normal adults — ages 30 to 89 — who had cognitive testing, magnetic resonance imaging, and fluorine 18–labeled florbetapir positron emission tomography imaging (to determine beta-amyloid levels in the brain) as part of the Dallas Lifespan Brain study.

The participants also had blood drawn to determine their ApoE genotype and had seven blood pressure measurements during study visits.

All told, 75 volunteers had normal blood pressure, but the normotensive and hypertensive groups were significantly different in age, so Rodrigue and colleagues excluded normotensive volunteers younger than 47 – the youngest age in the hypertensive group.

In the reduced cohort of 118 people, 69 had high blood pressure, including 54 who were medicated for the condition. If they carried at least one E4 allele, participants were classified as having genetic risk; 18.6 percent had one allele and 4.2 percent had two.

Analysis showed that hypertension and genetic risk had a significant interaction at P<0.05, the researchers reported.

Among those with normal blood pressure, the presence of the E4 allele made no difference in uptake of beta-amyloid, they found, but in the participants with high blood pressure, having the E4 allele meant a significant increase in beta-amyloid deposition.

When participants were stratified by genetic risk, there was no significant difference in amyloid burden by blood pressure among those without the E4 allele.

On the other hand, among those with the allele, normal blood pressure was associated with amyloid burden similar to the non-E4 group. Those with high blood pressure controlled by medication had a higher burden, but not significantly so.

But participants with unmedicated hypertension and the E4 allele had significantly higher levels of amyloid burden than all other groups, Rodrigue and colleagues reported.

Although more study is needed, "these initial findings suggest that individuals with an ApoE4 allele may be able to attenuate their likelihood for amyloid accumulation through proper control of blood pressure," the researchers argued.

Rodrigue and colleagues cautioned that the study was snapshot and can't say anything about cause and effect. As well, the study population is highly screened for a study of healthy aging, so the results may not apply more widely.

Source: Blood Pressure Control May Help Slow Alzheimer's