Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.79

March 23, 2020

Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 24 March 2020
Okayama University research: Novel blood-based markers to detect Alzheimer’s disease

(Okayama, 24 March) In a recent study published in the Journal of Alzheimer’s Disease, researchers at Okayama University developed a technique to uncover molecules within the blood which can help doctors differentiate patients with Alzheimer’s disease from healthy individuals.

Alzheimer’s disease (AD) is highly prevalent in regions with aging populations such as Japan, China, and Western Europe. The condition severely impairs one’s memory, cognitive abilities, and mood. Diagnosis of AD is tricky and forces neurologists to rely on a battery of tests. Additionally, AD is often confused with mild cognitive impairment (MCI), a milder version of the disease. A group led by Professor ABE Koji from the Department of Neurology at Okayama University has now identified molecules in the blood which can help discern patients with AD from those with MCI, as well as healthy individuals.

Besides examining symptoms closely, neurologists detect AD by measuring toxic proteins the brain and the cerebrospinal fluid (CSF)—a clear fluid that runs through the nervous system. However, extracting the CSF from patients involves a painful procedure. The research team, thus, used the blood—an easily extractable fluid—to investigate proteins that may aid with detection. Biochemists typically use a technique called ‘mass spectrometry’ to analyze proteins in the blood. However, the blood also contains some bulky proteins which can clog the instruments used in this technique. Ironically, removing these proteins also eliminates their docking partners known as peptides, which contain important information about an individual’s health status. Professor ABE’s team developed a method of separating the peptides from the bulky proteins and transferring the former on to a chip which can be analyzed on a sensitive mass spectrometer. Blood samples of AD patients, MCI patients, and healthy individuals were subsequently tested.

The blood peptides of these three groups did indeed appear different, with a set of four specific peptides showing the most varied patterns. These peptides appeared to be high in the AD patients, moderate in the MCI patients, and low in healthy individuals. As expected, these peptide levels also coincided with each individual’s cognitive performance on a clinical test. Individuals with higher peptides did worse on the test. When some individuals were subjected to brain scans, it was found that AD patients showing an accumulation of toxic proteins in their brains also had high peptides in their blood. Thus, patterns of the four peptides in the three groups were in sync with the other detection tests. Finally, a deeper delve into the biology of these peptides hinted that they were linked to inflammation in the brain.

“The present study provides a new diagnostic biomarker set for MCI and AD by a new peptidome technology, but also suggests an important pathomechanism of AD for neuroinflammation,” propose the researchers. While the blood peptides can be used as an easy and cheap method of diagnosing AD in the clinic, the peptide separation technology can be used for discovering markers for other diseases.

Alzheimer’s disease: Alzheimer’s disease affects more than 6.4 million people in Japan. The disease has no cure at present and therapeutic strategies can only impede its progression. In order to provide timely treatment, an accurate and early diagnosis is vital. Unfortunately, at present neurologists do not have one definitive method of detection. Brain scans and CSF extraction are also expensive and inconvenient techniques. Thus, the research community is directing their efforts at developing a blood-based detection test. Given that blood is easy to draw from patients, such tests can be repeated often and also performed periodically to monitor whether therapeutic strategies are working.

Koji Abe, Jingwei Shang, Xiaowen Shi, Toru Yamashita, Nozomi Hishikawa, Mami Takemoto, Ryuta Morihara, Yumiko Nakano, Yasuyuki Ohta, Kentaro Deguchi, Masaki Ikeda, Yoshio Ikeda, Koichi Okamoto, Mikio Shoji, Masamitsu Takatama, Motohisa Kojo, Takeshi Kuroda, Kenjiro Ono, Noriyuki Kimura, Etsuro Matsubara, Yosuke Osakada, Yosuke Wakutani, Yoshiki Takao, Yasuto Higashi, Kyoichi Asada, Takehito Senga, Lyang-Ja Lee, and Kenji Tanaka. A new serum biomarker set to detect mild cognitive impairment and Alzheimer’s disease by peptidome technology. Journal of Alzheimer's Disease, 2020;73(1):217-227.
DOI : 10.3233/JAD-191016.
A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology - IOS Press

Reference (Okayama Univ. e-Bulletin): Professor ABE’s team
OU-MRU Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury

Correspondence to
Professor ABE Koji, M.D., Ph.D.
Department of Neurology, Graduate School of Medicine,
Dentistry and Pharmaceutical Sciences, Okayama University,
2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan
E-mail: abekabek(a)cc.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
Department of Neurology and Neuroscience at Okayama University School of Medicine

Further information
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Okayama University Medical Research Updates (OU-MRU)
The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75:More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76:The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77:Green leafy vegetables contain a compound which can fight cancer cells
Vol.78:Disrupting blood supply to tumors as a new strategy to treat oral cancer