Immune blood biomarkers of Alzheimer disease patients.
Level 4 - case-series / case-control
Case-control diagnostic biomarker evaluation using non-consecutive clinical cohorts and convenience controls
PubMed 19329192 · doi:10.1016/j.jneuroim.2009.02.015
What was done
The authors evaluated a peripheral blood flow cytometric assay measuring amyloid-beta (Abeta) phagocytosis by macrophages to detect biomarkers for Alzheimer disease (AD) and mild cognitive impairment (MCI). Phagocytic capacity (<400 mean fluorescence intensity [MFI] defined as positive for impairment) was evaluated in AD patients, MCI patients, cognitively intact controls (active senior university professors), older caregivers, and older amyotrophic lateral sclerosis (ALS) patients. They also examined baseline and curcuminoid-stimulated transcriptional regulation of MGAT-III and TLR3 genes in patient macrophages.
What was found
- Abeta phagocytosis was impaired (<400 MFI) in 94% of AD patients (mean age 77 ± 2.2 years; mean score 198.6 ± 25.5 MFI) and 60% of MCI patients (mean age 77 ± 5.6 years; mean score 301 ± 106 MFI). - All healthy senior controls (100%) had normal phagocytosis (mean age 74.2 ± 4.2 years; mean score 1348 ± 174 MFI). - The assay exhibited low specificity when tested in older caregivers and older ALS patients. - Patients were classified into two transcriptional subtypes: Type I (majority) showed baseline down-regulation of MGAT-III and TLR3 that was up-regulated by curcuminoids, whereas Type II showed the opposite response.
Why it matters
The study shows that defective innate immune clearance of Abeta by peripheral blood macrophages correlates with cognitive impairment in AD and MCI, highlighting macrophage function as a potential blood-based diagnostic or prognostic target.
Limits
The abstract does not report the total sample size (n) for any evaluated cohort. The control group consisted of a non-representative convenience sample (active university professors). The assay showed poor disease specificity, with abnormal results observed in older caregivers and ALS patients. Prospective longitudinal validation is missing.
Cited by
- supports In a blood test developed by Milan Fiala at UCLA, peripheral blood mononuclear cells from Alzheimer's disease patients showed defective phagocytosis of amyloid-beta compared to healthy controls.