title: Alzheimer's senile plaque as shown by microcryodissection, a new technique for dissociating tissue structures.
abstract: Extracellular accumulation of Aβ peptides and intracellular aggregation of hyperphosphorylated tau proteins are the two hallmark lesions of Alzheimer disease (AD). The senile plaque is made of a core of extracellular Aβ surrounded by phospho-tau positive neurites. It includes multiple components such as axons, synapses, glial fibers and microglia. To visualize the relationships of those elements, an original technique was developed, based on the dilation of interstitial water during freezing. Samples of neocortex, hippocampus and striatum were taken from formalin-fixed brains (one control case; three cases with severe Alzheimer disease). The samples were subjected to various numbers of freezing/thawing cycles (from 0 to 320) with an automated system we devised. The samples were embedded in paraffin, cut and stained with haematoxylin-eosin or immunostained against Aβ, phospho-tau, and antigens enriched in axons, synapses, macrophages or astrocytes. Microcryodissection induced the dissociation of tissue components, especially in the grey matter where the neuropil formed an oriented "mesh". The size of the empty spaces separating the fiber bundles and cells increased with the number of cycles. The amyloid core of the senile plaque separated from its neuritic crown at around 300 freezing/thawing cycles. The dissected core remained associated with macrophages containing Aβ in their cytoplasm. Phospho-tau positive axons were distinctly seen projecting from the neuritic crown to the isolated amyloid core, where they ended in large synapses. The microcryodissection showed astrocytic processes stuck directly to the core. The original method we developed-microcryodissection-helped understanding how histological components were assembled in the tissue.
authors.affiliation: Alzheimer's and Prion Diseases Team, Institut du Cerveau et de la Moelle Epinière, CNRS UMR 7225, INSERM 1127, UPMC UM75, Paris, France. manon.thierry@icm-institute.org.|Laboratoire de Neuropathologie Raymond ESCOUROLLE, Paris, France. manon.thierry@icm-institute.org.
authors.forename: Manon
authors.initials: M
authors.lastname: Thierry
authors.affiliation: Alzheimer's and Prion Diseases Team, Institut du Cerveau et de la Moelle Epinière, CNRS UMR 7225, INSERM 1127, UPMC UM75, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Marty
authors.affiliation: Alzheimer's and Prion Diseases Team, Institut du Cerveau et de la Moelle Epinière, CNRS UMR 7225, INSERM 1127, UPMC UM75, Paris, France.|Laboratoire de Neuropathologie Raymond ESCOUROLLE, Paris, France.
authors.forename: Susana
authors.initials: S
authors.lastname: Boluda
authors.affiliation: Alzheimer's and Prion Diseases Team, Institut du Cerveau et de la Moelle Epinière, CNRS UMR 7225, INSERM 1127, UPMC UM75, Paris, France.|Laboratoire de Neuropathologie Raymond ESCOUROLLE, Paris, France.
authors.forename: Charles
authors.identifier: 0000-0001-9946-4611
authors.initials: C
authors.lastname: Duyckaerts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015925:Cryopreservation / Q000379:methods*; D005260:Female; D005615:Freezing; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D042282:Microdissection / Q000379:methods*; D008854:Microscopy, Electron; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010363:Pattern Recognition, Automated; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D014867:Water
chemical_list: D014867:Water
keywords: Alzheimer; Klingler’s method; Microcryodissection; Senile plaque