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P1‐008: BLOOD‐BASED BIOMARKERS OF ALZHEIMER'S DISEASE PATHOLOGY AND COGNITIVE DECLINE IN NON‐DEMENTED ELDERLY
Author(s) -
Westwood Sarah,
Leoni Emanuela,
Lynham Steven,
Khondoker Mizanur,
Kiddle Steven,
Sattlecker Martina,
Ashton Nicholas James,
Fuertes Ricardo Sainz,
Hye Abdul,
Bazenet Chantal,
Ward Malcolm,
Thambisetty Madhav,
Lovestone Simon
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.243
Subject(s) - neuropathology , atrophy , dementia , cognitive decline , medicine , amyloid (mycology) , cohort , disease , pathology , alzheimer's disease , alzheimer's disease neuroimaging initiative , biomarker , endophenotype , population , positron emission tomography , psychology , oncology , neuroscience , cognition , biology , environmental health , biochemistry
neuron-to-neuron. It is known that a-synuclein oligomers can transfer between cells but not if this requires neurites and synapses. We have previously visualized neuritic neuron-to-neuron transfer of b-amyloid, in an 3D co-culture system with differentiated neuron-like human SH-SY5Y cells. In this study we investigated if a-synuclein is transferred in a similar manner as b-amyloid.We also investigated the intracellular localization and toxicity of the transferred a-synuclein. Methods: Monomeric, oligomeric and fibrillar forms of a -synuclein were labeled with Cy3. SH-SY5Y neuroblastoma cells were extensively differentiated in an ECM gel with the addition of a cocktail of growth-factors and transfected with CellLight endosome-GFP (acceptor cells). Retinoic acid differentiated SH-SY5Y cells were incubated with 1-2 mM monomeric, oligomeric or fibrillary a-synuclein for 3 h (donor cells). Donor cells and acceptor cells were co-cultured for up to 7 days, fixed and analyzed using confocal microscopy. Results:Monomeric, oligomeric and fibrillar a-synuclein forms were taken up by donor cells within 3 hours and remained in the cells for at least 48 hours. After 24 h of co-culture, all tested forms of a-synuclein were transferred from donor cells to acceptor cells if neuritic connections were present. Oligomers were transferred more extensively than monomers. The a-synuclein co-localized with markers for multi vesicular bodies, endosoms and lysosomes. Conclusions: Monomeric, oligomeric and fibrillar forms of a-synuclein were transmitted through neuritic connections from donor to acceptor cells. The transfer of a-synuclein seem to involve multivesicular bodies as well as the endosomal and lysosomal compartments. The high level of differentiation of the acceptor cells, producing neuritic connections and synapses, seemed necessary for the transfer. Thus, we have found many similarities between a-synuclein and b-amyloid transfer.