Dataset Information

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

ABSTRACT: Degeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently discovered that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 (APOE4), exacerbates 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. Our analysis identified over 5,500 proteins in human synaptoneurosomes and highlighted disease and APOE-associated changes in multiple molecular pathways including a disruption of cellular and synaptic signalling, glial related protein changes important for neuroinflammatory neuron-glia interactions, and changes in proteins important for mitochondrial function in AD that differ with APOE genotype.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain, Synapse

DISEASE(S): Alzheimer's Disease

SUBMITTER: Douglas Lamont

LAB HEAD: Tara Spires-Jones

PROVIDER: PXD013753 | Pride | 2020-05-26

REPOSITORIES: Pride

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

Hesse Raphael R Hurtado Maica Llavero ML Jackson Rosemary J RJ Eaton Samantha L SL Herrmann Abigail G AG Colom-Cadena Marti M Tzioras Makis M King Declan D Rose Jamie J Tulloch Jane J McKenzie Chris-Anne CA Smith Colin C Henstridge Christopher M CM Lamont Douglas D Wishart Thomas M TM Spires-Jones Tara L TL

Acta neuropathologica communications 20191220 1

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, ...[more]

PMID: 31862015

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