Prof. Tengfei Guo took part in 2021 Alzheimer's Disease (AD) New Progress International Forum online as an invited guest.

During the conference, the first person to unify the concept of SCD in the world, Professor Frank Jessen from the University of Cologne Medical School in Germany brought us the relevant content and the introduction of the research results of the "DELCODE cohort study, the second stage of AD in the cognitive and biological characteristics". 

Prof. Guo’s questions and answers on Professor Jessen’s report are the highlights of this conference.

Guo: Good morning, Professor Jessen, thank you for your wonderful report! Thank you for your data sharing on the subjective cognitive decline in Germany. I have a few questions that I would like to ask you. I found in your report that older people with SCD over 80 are more likely to develop non-AD dementia in the future. Can you explain the possible reasons?

Frank: This is a very good question! Thank you for your attention to the details in my report. I think SCD over 80 years old has a high probability of suffering from mixed dementia, such as vascular disease and other diseases. Old people with SCD are more likely to be affected by other vascular factors besides the pathological features of AD, while young people with SCD are more likely to be affected by pathological features of AD.

Guo: Thank you very much! I have another problem. Compared with the elderly with normal amyloid-negative cognition, the hippocampal volume of the elderly with normal amyloid-positive cognition tends to be larger; however, the hippocampal volume of the elderly with amyloid-positive SCD is decreasing. Can you explain the reason behind this?

Frank: This is another very good question! When I showed it, I didn't emphasize this discovery. Our research group discussed this issue at the group meeting this morning. Our explanation is this. Normal elderly people who are positive for amyloid do not have any clinical symptoms or symptoms of SCD. They are likely to recognize it before the appearance of SCD. Knowing the performance of cognitive flexibility, cognitive flexibility may cause the hippocampus volume to increase, reduce the damage of amyloid plaques to the hippocampus volume, and avoid cognitive decline. This is our explanation for this problem.

Guo: Thank you very much! Have you looked at the relationship between amyloid plaques and hippocampal volume in the elderly with normal amyloid positive cognition? I think another reason may be that when amyloid plaques accumulate in the cerebral cortex, they may cause neuroinflammation. The emergence of neuroinflammation may cause neuronal cell hypertrophy, which will enlarge the brain structure.

Frank: This is a great idea! We have neuroinflammation biomarkers based on blood and cerebrospinal fluid. We will try to see the role of neuroinflammation biomarkers in it. This is a good suggestion.

Guo: Okay, thank you for your answer!

Prof. Guo analyzed "APOE-ε4 regulates the relationship between vascular disease, plasma Aβ42/Aβ40, neurodegenerative diseases, and cognitive decline in the elderly." With the introduction of the biological definition of AD, the objective evaluation of AD becomes possible. PET/MR assessment is relatively expensive, and it is relatively difficult to obtain cerebrospinal fluid. Prof Guo's research focuses on the biomarkers of plasma samples. They confirmed that plasma Aβ42/Aβ40 can predict the abnormality of cerebrospinal fluid Aβ42/Aβ40, and the accuracy increases with age. At the same time, the prediction accuracy of APOE-ε4 carriers will be higher than that of non-carriers. Similar liquid mass spectrometry (LC-MS/MS) methods are more sensitive than SIMOA and ELISA. In addition, plasma Aβ42/Aβ40 and white matter hyperintensity (WMH) can also predict long-term neuronal degeneration and cognitive decline.

Finally, Prof. Guo concluded that plasma LC-MS/MS and Aβ42/Aβ40 may have potential clinical application prospects for screening APOE-ε4 carriers in future clinical trials.