Abnormal lipid accumulation and cluster formation of naive peripheral blood mononuclear cells: a useful tool for early detection of central nervous system damage in elderly

Background: There is a great need for new research models, which are simple and accessible diagnostic procedures, in order to monitor the progression of suspected age-related neurological disorders. Objective: To determine whether changes in neutral lipids (NLs), and in the ability to form clusters, represent early events occurring in freshly isolated (naïve) peripheral blood mononuclear cells (PBMCs) from aged subjects affected by different neurological disorders. Methods: We examined 192 subjects, ≥ 65 years old, attending the outpatient services of the geriatric care unit for geriatric check-up, analysing NLs by Oil Red O (ORO) staining method, and the cluster formation (CF) rate of PBMCs. Results: ORO score was higher in PBMCs from subjects with any type of dementia than in PBMCs from healthy controls (HC). ORO score did not differ significantly between Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD), but in mild cognitive impairment (MCI) it was significantly higher than in HC, and significantly lower than in AD, MD and VD. There was also significant inverse correlation between ORO staining and Mini Mental State Examination (MMSE). The percentage of ORO staining intensity, calculated as a percentage of positively stained total cell area, was significantly lower in PBMCs from HC than in those from MCI and dementia. Furthermore, PBMCs from demented patients and MCI groups tend to aggregate in vitro to form cellular clusters: CF rate showed a similar pattern to that of ORO staining. Subjects with dementia but not vision problems had lower ORO staining and CF scores than subjects with both eye disorders and dementia. Conclusion: We suggest that the presence of NLs in the cytoplasm of unstimulated PBMCs, combined with their potential tendency to form clusters, may represent a novel, non-invasive approach to detecting and monitoring neuronal injury in the early stages of disease.