Endosomal compartment modifications in peripheral cells point to AD biomarker
medwireNews: Researchers have found endosomal compartment modifications in the peripheral blood mononuclear cells (PBMCs) of patients with Alzheimer’s disease (AD) that correlate with amyloid load and may represent a biomarker for the condition.
“[W]e found morphological alterations of the endosomal compartment in the blood cells (PBMCs) from sporadic biologically confirmed AD patients as well as in fibroblasts of clinically defined independent sporadic AD patients”, the team reports in Translational Psychiatry.
PBMCs were purified from the blood of 48 patients with AD – 25 with mild cognitive impairment and 23 with dementia – and 23 individuals without dementia and matched for age.
The early endosomes present, which were stained by immunohistochemistry using an antibody against early endosome antigen 1, were similar in number and volume among the three groups.
But the researchers note that further analysis of the endosome size distribution showed that patients with AD had a significantly higher percentage of cells containing enlarged endosomes compared with healthy individuals.
Specifically, 17.4% of the 455 cells from the AD group and 13.5% of 497 cells from the mild cognitive impairment patients contained endosomes measuring above the ninth decile, at more than 0.412 µM3, compared with just 10.0% of those from healthy individuals.
Researchers Marie-Claude Potier (UPMC, Sorbonne Universités, Paris, France) and Marie Sarazin (Université Paris Descartes, France) and colleagues confirmed the stability of the distinction between the AD groups and controls by drawing 1000 bootstrap samples at the individual level.
They point out that a distinction from controls was evident even in the patients with mild cognitive impairment who have an early stage of the disease.
The differences in endosomal volumes also correlated positively with amyloid burden, as assessed by positron emission tomography using [C11]Pittsburgh compound B retention
“Notably this correlation was still valid after conditioning with age and APOE ε4 status”, report the researchers, who add that further study is needed to determine whether such changes in the morphology of early endosomes are specific to AD or occur in other neurological diseases.
The researchers went on to confirm the presence of abnormally large endosomes in AD in a second peripheral cell type – fibroblasts.
Of 90 fibroblasts from six patients with AD, 26.7% contained larger endosomes, at a mean volume of at least 0.191 µM3, compared with 10.5% of 76 cells in five age-matched controls.
“[A]s fibroblasts also carry this enlarged endosome phenotype, we believe that endosomal changes are more likely to be present in a small percentage of all cell types of PBMCs rather than a specific subpopulation”, the researchers say.
They call for further studies to determine how these endosomal changes evolve during the course of the disease and whether endosome biomarkers, either cellular or plasmatic, can be identified.
By Lucy Piper
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