Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease.
BACKGROUND
Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives.


METHODS
Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean +/- standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test.


RESULTS
Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (ex vivo) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients.


CONCLUSIONS
We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.
Pani
Alessandra
A
Department of Internal Medical Science, University of Cagliari, Italy. pania@unica.it
Mandas
Antonella
A
Diaz
Giacomo
G
Abete
Claudia
C
Cocco
Pier Luigi
PL
Angius
Fabrizio
F
Brundu
Annalisa
A
Muçaka
Nico
N
Pais
Maria Elena
ME
Saba
Antonio
A
Barberini
Luigi
L
Zaru
Cristina
C
Palmas
Manuela
M
Putzu
Paolo F
PF
Mocali
Alessandra
A
Paoletti
Francesco
F
La Colla
Paolo
P
Dessì
Sandra
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D015415:Biomarkers; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism*; D010949:Plasma / Q000737:chemistry; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014481:United States; D055815:Young Adult
D015415:Biomarkers; D008076:Cholesterol, HDL; D010743:Phospholipids