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Serum folate levels, RBC content potential biomarkers for Alzheimer’s

Tristan Manalac
18 Apr 2017

Serum folate levels in combination with red blood cell (RBC) haemoglobin content is a better biomarker for Alzheimer’s disease (AD) and brain accumulation of amyloid β than folate or apolipoprotein E (APOE) alone, a new study reveals.

The investigators subjected 17 patients (10 female; mean age 77.1±6.5 years) to magnetic resonance imaging and positron emission tomography (PET) scanning to determine amyloid β load in the brain. Individuals diagnosed with dementia were recruited regardless of age and sex.

Chemiluminescent enzyme immunoassays and a haematology analyser were used to measure the serum folate and RBC haemoglobin content, respectively. Polymorphisms in the APOE gene were analyzed using the invader method.

Of the 17 participants, 10 were AD patients while seven had mild cognitive impairment (MCI); 11 tested positive for amyloid β. The mean serum folate levels were 7.8±4.6, 6.2±3.6 and 10.7±5.3 ng/mL for all participants, amyloid positive and amyloid negative participants, respectively. Their respective mean haemoglobin contents were 12.8±1.9, 13.6±1.5 and 11.4±1.8 g/dL. [PLoS One 2017;doi:10.1371/journal.pone.0175854]

The APOE-epsilon 4 allele was reported in nine of the 17 participants. The APOE-epsilon 4 allele was found in eight and one of those who tested positive and negative for amyloid β, respectively.

According to the receiver operative curve (ROC) analysis, those with low levels of serum folate had a higher chance of testing positive for amyloid β (area under the ROC curve [AUC], 0.136; 95 percent CI, 0.000 to 0.312; p=0.016).

Haemoglobin content has high diagnostic value when used as an auxiliary diagnostic tool to serum folate (AUC, 0.848; 0.661 to 1.000; p=0.021), indicating that individuals with nonanaemia with high haemoglobin content are more likely to also test positive for amyloid β. Nonanaemia and folate deficiency was observed in 87.5 percent (n=7) and 12.5 percent (n=1) of amyloid positive and negative patients, respectively.

There was a significant difference in the incidence of the APOE-epsilon 4 allele between amyloid positive (72.7 percent) and amyloid negative (16.7 percent; p=0.027).

Finally, all of the APOE-epsilon 4 carriers with nonanaemia and folate deficiency tested positive for amyloid and all of the noncarrier, nonfolate deficient individuals with anaemia tested negative for amyloid indicating “that these biomarkers could enhance the effectiveness of APOE as an AD biomarker,” the investigators explained.

“[T]he combined assessment of serum folate levels and blood cell haemoglobin content may be an accurate blood biomarker of amyloid β accumulation in the brain and may have the potential to compensate for the relative weakness of APOE as an AD biomarker,” they added.

Because of its current limitations, future studies that involve larger samples and healthy controls are required before complete diagnostic protocols are established. Regardless, the findings presented in the study could be used to “support clinical diagnosis using a simple and easy blood test,” researchers said.

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