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.
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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.
Perspectives
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.
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Resources
Senile plaques in Alzheimer’s disease are primarily induced by cerebral vessel leakage of red blood cells and other blood contents
The second preprint of this study released in May 2020. We proposed that microaneurysm rupture-induced blood Aβ lekage could be a way of senile plaque formation.
Senile plaques in Alzheimer’s disease arise from Cathepsin D and Aβ-enriched proteinaceous mixtures out of hemolysis and vascular degeneration
The third preprint of this study, released in May 2021. The importance of Cathepesin D in hemolyis and senile plaque formation was highlighted.
Senile plaques in Alzheimer’s disease arise from Aβ and Cathepsin D-enriched amyloidogenic mixtures out of intravascular hemolysis and Charcot-Bouchard aneurysm-related vascular degeneration
The fourth preprint of this study, released in Oct. 2022. Microaneurysm rupture-induced blood Aβ lekage leading to senile plaque formation was proved.
Re-evaluating the nuclear staining on pathological sections in Alzheimer's disease
This manuscript addressed a potentially common problem of mistaking senile plaque blue autofluorescence as nuclear staining in Alzheimer's disease research.
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