Abbood AS, Faisal AJ, Hussein MS (2025) The role of tissue biopsy in diagnosing Alzheimer’s disease: histological perspectives. J Med Life Sci 7:114–126. https://doi.org/10.21608/jmals.2025.348212.1038

Google Scholar 

Abe M, Ohno N (2025) Recent advancement and human tissue applications of volume electron microscopy. Microscopy 74:233–243. https://doi.org/10.1093/jmicro/dfae047

Google Scholar 

Abskharon R, Sawaya MR, Boyer DR et al (2022) Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation. Proc Natl Acad Sci U S A 119:e2119952119. https://doi.org/10.1073/pnas.2119952119

Google Scholar 

Adlimoghaddam A, Fayazbakhsh F, Mohammadi M et al (2025) Sex and region-specific disruption of autophagy and mitophagy in Alzheimer’s disease: linking cellular dysfunction to cognitive decline. Cell Death Discov 11:204. https://doi.org/10.1038/s41420-025-02490-0

Google Scholar 

Ahmadi S, Zhu S, Sharma R et al (2019) Interaction of metal ions with tau protein. The case for a metal-mediated tau aggregation. J Inorg Biochem 194:44–51. https://doi.org/10.1016/j.jinorgbio.2019.02.007

Google Scholar 

Alfaro-Ruiz R, Aguado C, Martín-Belmonte A et al (2022) Alteration in the synaptic and extrasynaptic organization of AMPA receptors in the hippocampus of P301S tau transgenic mice. IJMS 23:13527. https://doi.org/10.3390/ijms232113527

Google Scholar 

Alkhalifa AE, Al-Ghraiybah NF, Odum J et al (2023) Blood–brain barrier breakdown in Alzheimer’s disease: mechanisms and targeted strategies. Int J Mol Sci 24:16288. https://doi.org/10.3390/ijms242216288

Google Scholar 

Androuin A, Potier B, Nägerl UV et al (2018) Evidence for altered dendritic spine compartmentalization in Alzheimer’s disease and functional effects in a mouse model. Acta Neuropathol 135:839–854. https://doi.org/10.1007/s00401-018-1847-6

Google Scholar 

Arimoto E, Kawashima Y, Choi T et al (2019) Analysis of a cellular structure observed in the compound eyes of Drosophila white; yata mutants and white mutants. Biol Open Bio. https://doi.org/10.1242/bio.047043

Google Scholar 

Baena V, Schalek RL, Lichtman JW, Terasaki M (2019) Serial-section electron microscopy using automated tape-collecting ultramicrotome (ATUM). Methods in Cell Biology. Elsevier, Amsterdam, pp 41–67

Google Scholar 

Beretta C, Svensson E, Dakhel A et al (2024) Amyloid-β deposits in human astrocytes contain truncated and highly resistant proteoforms. Mol Cell Neurosci 128:103916. https://doi.org/10.1016/j.mcn.2024.103916

Google Scholar 

Bisht K, El Hajj H, Savage JC et al (2016a) Correlative light and electron microscopy to study microglial interactions with & #946;-amyloid plaques. JoVE. https://doi.org/10.3791/54060

Google Scholar 

Bisht K, Sharma KP, Lecours C et al (2016b) Dark microglia: a new phenotype predominantly associated with pathological states. Glia 64:826–839. https://doi.org/10.1002/glia.22966

Google Scholar 

Booth DS, Avila-Sakar A, Cheng Y (2011) Visualizing proteins and macromolecular complexes by negative stain EM: from Grid preparation to image Acquisition. JoVE. https://doi.org/10.3791/3227

Google Scholar 

Brainbank NeuroCEB Neuropathology Network, Androuin A, Thierry M et al (2022) Alterations of neuronal lysosomes in Alzheimer’s disease and in APPxPS1-KI mice. J Alzheimers Dis 87:273–284. https://doi.org/10.3233/JAD-215692

Google Scholar 

Burgess SA, Walker ML, Thirumurugan K et al (2004) Use of negative stain and single-particle image processing to explore dynamic properties of flexible macromolecules. J Struct Biol 147:247–258. https://doi.org/10.1016/j.jsb.2004.04.004

Google Scholar 

Cai Q, Jeong YY (2020) Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells 9:150. https://doi.org/10.3390/cells9010150

Google Scholar 

Calì C, Wang X (2025) Editorial: advances in volume electron microscopy for brain imaging: methods, applications, and affordability. Front Neurosci 19:1561852. https://doi.org/10.3389/fnins.2025.1561852

Google Scholar 

Castaño EM, Ghiso J, Prelli F et al (1986) In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to alzheimer’s disease β-protein. Biochem Biophys Res Commun 141:782–789. https://doi.org/10.1016/S0006-291X(86)80241-8

Google Scholar 

Collingwood JF, Chong RKK, Kasama T et al (2008) Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer’s plaque core material. JAD 14:235–245. https://doi.org/10.3233/JAD-2008-14211

Google Scholar 

Collinson LM, Bosch C, Bullen A et al (2023) Volume EM: a quiet revolution takes shape. Nat Methods 20:777–782. https://doi.org/10.1038/s41592-023-01861-8

Google Scholar 

Cozachenco D, Ribeiro FC, Ferreira ST (2023) Defective proteostasis in Alzheimer’s disease. Ageing Res Rev 85:101862. https://doi.org/10.1016/j.arr.2023.101862

Google Scholar 

Creekmore BC, Chang Y-W, Lee EB (2021) The cryo-EM effect: structural biology of neurodegenerative disease aggregates. J Neuropathol Exp Neurol 80:514–529. https://doi.org/10.1093/jnen/nlab039

Google Scholar 

Creekmore BC, Kixmoeller K, Black BE et al (2024a) Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling. Nat Commun 15:2660. https://doi.org/10.1038/s41467-024-47066-1

Google Scholar 

Creekmore BC, Watanabe R, Lee EB (2024b) Neurodegenerative disease tauopathies. Annu Rev Pathol Mech Dis 19:345–370. https://doi.org/10.1146/annurev-pathmechdis-051222-120750

Google Scholar 

Crowther RA (2021) Insights into neurodegeneration from electron microscopy studies. Biochem Soc Trans 49:2777–2786. https://doi.org/10.1042/BST20210719

Google Scholar 

Crowther RA, Goedert M (2000) Abnormal tau-containing filaments in neurodegenerative diseases. J Struct Biol 130:271–279. https://doi.org/10.1006/jsbi.2000.4270

Google Scholar 

Cuadrado-Tejedor M, Pérez-González M, Alfaro-Ruiz R et al (2021) Amyloid-driven tau accumulation on mitochondria potentially leads to cognitive deterioration in Alzheimer’s disease. IJMS 22:11950. https://doi.org/10.3390/ijms222111950

Google Scholar 

Dasari AKR, Bhatt N, Haque MA et al (2025) Cryo-EM structural analyses reveal diverse porous structures in brain-derived tau oligomers. Biochem Biophys Res Commun 776:152189. https://doi.org/10.1016/j.bbrc.2025.152189

Google Scholar 

de Wil MC, Overk CR, Sijben JW, Masliah E (2016a) Meta‐analysis of synaptic pathology in Alzheimer’s disease reveals selective molecular vesicular machinery vulnerability. Alzheimer’s Dementi 12:633–644. https://doi.org/10.1016/j.jalz.2015.12.005

Google Scholar 

de Wil MC, Overk CR, Sijben JW, Masliah E (2016b) Meta‐analysis of synaptic pathology in Alzheimer’s disease reveals selective molecular vesicular machinery vulnerability. Alzheimers Dement 12:633–644. https://doi.org/10.1016/j.jalz.2015.12.005

Google Scholar 

DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464. https://doi.org/10.1002/ana.410270502

Google Scholar 

Del Prete D, Suski JM, Oulès B et al (2016) Localization and processing of the amyloid-β protein precursor in mitochondria-associated membranes. JAD 55:1549–1570. https://doi.org/10.3233/JAD-160953

Google Scholar 

Dhiman N, Deshwal S, Rishi V et al (2025) Zebrafish as a model organism to study sporadic Alzheimer’s disease: behavioural, biochemical and histological validation. Exp Neurol 383:115034. https://doi.org/10.1016/j.expneurol.2024.115034

Google Scholar 

Domínguez-Álvaro M, Montero-Crespo M, Blazquez-Llorca L et al (2018) Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer’s disease patients. Acta Neuropathol Commun 6:20. https://doi.org/10.1186/s40478-018-0520-6

Google Scholar 

Domínguez-Álvaro M, Montero-Crespo M, Blazquez-Llorca L et al (2019) 3D electron microscopy study of synaptic organization of the normal human transentorhinal cortex and its possible alterations in Alzheimer’s disease. eNeuro 6:ENEURO.0140-19.2019. https://doi.org/10.1523/ENEURO.0140-19.2019

Google Scholar 

Dujardin S, Hyman BT (2019) Tau Prion-Like Propagation: State of the Art and Current Challenges. In: Takashima A, Wolozin B, Buee L (eds) Tau Biology. Springer Singapore, Singapore, pp 305–325

Dyne E, Cawood M, Suzelis M et al (2022) Ultrastructural analysis of the morphological phenotypes of microglia associated with neuroinflammatory cues. J Comp Neurol 530:1263–1275. https://doi.org/10.1002/cne.25274

Google Scholar 

Eberle AL, Zeidler D (2018) Multi-beam scanning electron microscopy for high-throughput imaging in connectomics research. Front Neuroanat 12:112. https://doi.org/10.3389/fnana.2018.00112

Google Scholar 

Eitan E, Thornton-Wells T, Elgart K et al (2023) Synaptic proteins in neuron-derived extracellular vesicles as biomarkers for Alzheimer’s disease: novel methodology and clinical proof of concept. Extracell Vesicles Circ Nucleic Acids 4:133–150. https://doi.org/10.20517/evcna.2023.13

Google Scholar 

El Hajj H, Savage JC, Bisht K et al (2019) Ultrastructural evidence of microglial heterogeneity in Alzheimer’s disease amyloid pathology. J Neuroinflammation 16:87. https://doi.org/10.1186/s12974-019-1473-9

Google Scholar 

Everett J, Brooks J, Lermyte F et al (2020) Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42). Sci Rep 10:10332. https://doi.org/10.1038/s41598-020-67117-z

Google Scholar 

Falcon B, Zhang W, Schweighauser M et al (2018) Tau filaments from multiple cases of sporadic and inherited Alzheimer’s disease adopt a common fold. Acta Neuropathol 136:699–708. https://doi.org/10.1007/s00401-018-1914-z

Google Scholar 

Fernandez A, Hoq MR, Hallinan GI et al (2024) Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. Nat Struct Mol Biol 31:903–909. https://doi.org/10.1038/s41594-024-01252-3

Google Scholar 

Fitzpatrick AWP, Falcon B, He S et al (2017) Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547:185–190. https://doi.org/10.1038/nature23002

Google Scholar 

Fowler SL, Behr TS, Turkes E et al (2025) Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease. Nat Neurosci 28:40–48. https://doi.org/10.1038/s41593-024-01801-5

Google Scholar 

Frieg B, Han M, Giller K et al (2024) Cryo-EM structures of lipidic fibrils of amyloid-β (1-40). Nat Commun 15:1297. https://doi.org/10.1038/s41467-023-43822-x

Google Scholar 

Frisoni GB, Altomare D, Thal DR et al (2022) The probabilistic model of Alzheimer disease: the amyloid hypothesis revised. Nat Rev Neurosci 23:53–66. https://doi.org/10.1038/s41583-021-00533-w

Google Scholar 

Fujimoto K (1995) Freeze-fracture replica electron microscopy combined with sds digestion for cytochemical labeling of integral membrane proteins: application to the immunogold labeling of intercellular junctional complexes. J Cell Sci 108:3443–3449. https://doi.org/10.1242/jcs.108.11.3443

Google Scholar 

Gárate-Vélez L, Escudero-Lourdes C, Salado-Leza D et al (2020) Anthropogenic iron oxide nanoparticles induce damage to brain microvascular endothelial cells forming the blood-brain barrier. JAD 76:1527–1539. https://doi.org/10.3233/JAD-190929

Google Scholar 

Ghosh U, Thurber KR, Yau W-M, Tycko R (2021) Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer’s disease brain tissue. Proc Natl Acad Sci USA 118:e2023089118. https://doi.org/10.1073/pnas.2023089118

Google Scholar 

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