Pathological axonal enlargement in connection with amyloidosis,lysosome destabilization,and bleeding is a major defect in Alzheimer’s diseaseOA
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
Hualin Fu;Jilong Li;Chunlei Zhang;Guo Gao;Qiqi Ge;Xinping Guan;Daxiang Cui
Institute of Nano Biomedicine and Engineering,School of Sensing Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University,Shanghai,China Institute of Marine Equipment,Shanghai Jiao Tong University,Shanghai,China National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai,ChinaInstitute of Nano Biomedicine and Engineering,School of Sensing Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaInstitute of Nano Biomedicine and Engineering,School of Sensing Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University,Shanghai,China National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai,ChinaInstitute of Nano Biomedicine and Engineering,School of Sensing Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University,Shanghai,China National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai,ChinaInstitute of Marine Equipment,Shanghai Jiao Tong University,Shanghai,China Department of Automation,Shanghai Jiao Tong University,Shanghai,ChinaDepartment of Automation,Shanghai Jiao Tong University,Shanghai,China The Key Laboratory of System Control and Information Processing,Ministry of Education,Shanghai,ChinaInstitute of Nano Biomedicine and Engineering,School of Sensing Science and Engineering,School of Electronic Information and Electrical Engineering,Shanghai Jiao Tong University,Shanghai,China National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai,China
医药卫生
Alzheimer’s diseaseamyloid-βamyloidosisaxonal enlargementhemoglobinhemorrhagelysosome destabilizationneuropil threadtauWallerian degeneration
《Neural Regeneration Research》 2026 (2)
P.790-799,10
supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
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