Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype

Raphael Hesse, Maica Llavero Hurtado, Rosemary J. Jackson, Samantha L. Eaton, Abigail G. Herrmann, Marti Colom-Cadena, Makis Tzioras, Declan King, Jamie Rose, Jane Tulloch, Chris-Anne McKenzie, Colin Smith, Christopher M. Henstridge, Douglas Lamont, Thomas M. Wishart, Tara L. Spires-Jones

Research output: Contribution to journalArticlepeer-review


Degeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently observed that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 (APOE4), is associated with exacerbated synapse loss and synaptic accumulation of oligomeric amyloid beta in human AD brain. To begin to understand the molecular cascades involved in synapse loss in AD and how this is mediated by APOE, and to generate a resource of knowledge of changes in the synaptic proteome in AD, we conducted a proteomic screen and systematic in silico analysis of synaptoneurosome preparations from temporal and occipital cortices of human AD and control subjects with known APOE gene status. We examined brain tissue from 33 subjects (7–10 per group). We pooled tissue from all subjects in each group for unbiased proteomic analyses followed by validation with individual case samples. Our analysis identified over 5500 proteins in human synaptoneurosomes and highlighted disease, brain region, and APOE-associated changes in multiple molecular pathways including a decreased abundance in AD of proteins important for synaptic and mitochondrial function and an increased abundance of proteins involved in neuroimmune interactions and intracellular signaling.
Original languageEnglish
Article number214
Number of pages18
JournalActa Neuropathologica Communications
Early online date20 Dec 2019
Publication statusE-pub ahead of print - 20 Dec 2019


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