Currently, best-characterized indicators for Alzheimer’s disease (AD) diagnosis are the decreased levels of amyloid β-protein 42 and increased levels of phosphorylated tau in cerebrospinal fluid (CSF). The positron emission tomography (PET) imaging with Pittsburgh compound B (PiB) is also used in AD diagnosis by visualizing amyloid deposition in the brain. Because these methods are invasive or expensive, less invasive and easily detectable blood biomarkers are required.
A team of researchers from Nagoya City University and other institutions have discovered a method that may pave the way for early diagnosis of Alzheimer’s disease using a blood test.
Members of the team said Tuesday that the number of exosomes — vesicles that mediate intercellular communication — is reduced in Alzheimer’s patients. So, therefore, a decrease in a protein called flotillin, a marker of exosomes, contained in blood is a key indicator of the disease.
“Flotillin detected in less than a drop of blood enables a diagnosis of Alzheimer’s disease and mild cognitive impairment at a stage prior to the disease,” said Prof. Makoto Michikawa of Nagoya City University.
Serum flotillin levels in autopsy cases with AD were lower
than those in cases with vascular dementia (VD)
Western blot analysis of serum obtained from autopsy cases with AD and VD was performed according to the methods described in the Methods section. A, Representative Western blot of flotillin in serum from the autopsy cases with AD and VD. B, The intensities of flotillin bands were measured using Image J and the intensity of each band was normalized by the average value of samples from cases with VD as 1. The serum flotillin levels significantly decreased in cases with AD compared with cases with VD. VD group, n=17; AD group, n=20. Data are mean ± S.E.M. Statistical analysis was performed by ANOVA.
The team is currently working with a company to improve its method for detecting flotillin, aiming for practical use of a blood test as an easier and less costly method compared to other techniques such as positron emission tomography, or PET, according to Michikawa.
It is already known that an abnormal protein, called amyloid beta, starts to accumulate as deposits in the brain of an Alzheimer’s patient over a 20-year period before symptoms appear.
By conducting PET tests on Alzheimer’s patients, the team discovered that as more deposits are formed in the brain, the number of exosomes secreted from nerves and other cells are reduced, leading to a decline in flotillin levels in the cerebrospinal fluid and serum.
Source – The Japan Times