What is it about?

A prominent feature of Alzheimer’s disease is the formation of senile plaques in the brain. Amyloid beta (Aβ) is a major component of the senile plaque. It is not clear how senile plaque forms and we don’t know what the physiological function of Aβ is. This study showed that Aβ binds red blood cell (RBC) directly and participates in red blood cell stress response and is abundantly present in intravascular hemolysates. Aβ-interacting RBC aggregates and vascular amyloid plaques block the blood flow in small cerebral vessels, which further associates with cerebral amyloid angiopathy (CAA) and microaneurysm development. Microaneurysms contain high concentrations of amyloid beta peptide, serving as the major sites of amyloid formation. Microaneurysm rupture and chronic leakage of Aβ-enriched hemolysates induces the formation of senile plaques of all forms such as dense-core plaques and diffusive plaques.

Featured Image

Why is it important?

Firstly, this study suggests that Aβ is an important blood homeostasis modulator. Secondly, this study helps to solve the long-debated pathological mechanism of senile plaque formation in Alzheimer’s disease. Thirdly,the research points to several critical stages that we can tackle the disease such as RBC stress, blood coagulation, vascular integrity and calcium signaling. In summary,Aβ-related blood and vascular defects likely happend before neuronal defects in Alzheimer's disease.


I hope this article can help people to take a fresh look at the root cause of Alzheimer’s disease. I was thinking that this disease has to be tightly linked to the aging process itself for over 10 years. As the study indicates, AD is a blood and vascular-related systematic disease bearing significant neuronal phenotypes. This article additionally provides reasonable explanations on the development of some common related medical phenomena, such as "increased perivascular space", "CAA", “microaneurysm” and "blood vessel calcification".

Dr. Hualin Fu
Shanghai Jiao Tong University

Read the Original

This page is a summary of: Senile plaques in Alzheimer's disease arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular hemolysis and microaneurysm rupture, FEBS Letters, November 2022, Wiley,
DOI: 10.1002/1873-3468.14549.
You can read the full text:




The following have contributed to this page