Senile plaques in Alzheimer's disease arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture. Issue 7 (12th December 2022)

• Record Type: Journal Article
• Authors: Fu, Hualin; Li, Jilong; Du, Peng; Jin, Weilin; Gao, Guo; Cui, Daxiang
• Is Part Of: FEBS letters. Volume 597:Issue 7(2023)
• Page Start: 1007
• Page End: 1040
• Publication Date: 2022-12-12
• Subjects: Alzheimer's disease -- Aβ -- Cathepsin D -- intravascular haemolysis -- microaneurysm -- senile plaque; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14549
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Senile plaques are a pathological hallmark of Alzheimer's disease (AD), yet the mechanism underlying their generation remains unknown. Beta‐amyloid peptide (Aβ) is a major component of senile plaques. We analysed AD brain tissues with histochemistry, immunohistochemistry and fluorescence imaging to examine the neural, vascular or blood Aβ contribution to senile plaque development. We found little neural marker co‐expression with plaque Aβ, while co‐expression of blood markers, such as Haemin and ApoE, was abundant. The plaque cores were structured with vascular and glial proteins outside and blood metabolites inside, co‐localizing with a characteristic of Hoechst staining‐independent blue autofluorescence. Erythrocyte‐interacting Aβ is linked to coagulation, elevated calcium and blue autofluorescence, and it is associated with intravascular haemolysis, atherosclerosis, cerebral amyloid angiopathy, microaneurysm, and often with Cathepsin D co‐expression. We identified microaneurysms as major sites of amyloid formation. Our data suggest that senile plaques arise from Aβ‐ and Cathepsin D‐enriched mixtures leaking out during intravascular haemolysis and microaneurysm rupture. Abstract : Our findings show that in Alzheimer's disease, the blood flow in blood vessels is intermitted by red blood cell aggregates and haemolytic amyloid plaques enriched with Aβ. The blood flow blockade is associated with fusiform and saccular microaneurysm formation. The chronic microaneurysm rupture and chronic hemolysate leakage lead to the formation of senile plaques of all forms, such as dense‐core and diffusive senile plaques.