Changes in the detergent-insoluble brain proteome linked to amyloid and tau in Alzheimer's Disease progression.

ABSTRACT: Despite a key role of amyloid-beta (A?) in Alzheimer's disease (AD), mechanisms that link A? plaques to tau neurofibrillary tangles and cognitive decline still remain poorly understood. The purpose of this study was to quantify proteins in the sarkosyl-insoluble brain proteome correlated with A? and tau insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry-based proteomics, we quantified 2711 sarkosyl-insoluble proteins across the prefrontal cortex from 35 individual cases representing control, AsymAD, MCI and AD. Significant enrichment of A? and tau in AD was observed, which correlated with neuropathological measurements of plaque and tau tangle density, respectively. Pairwise correlation coefficients were also determined for all quantified proteins to A? and tau, across the 35 cases. Notably, six of the ten most correlated proteins to A? were U1 small nuclear ribonucleoproteins (U1 snRNPs). Three of these U1 snRNPs (U1A, SmD and U1-70K) also correlated with tau consistent with their association with tangle pathology in AD. Thus, proteins that cross-correlate with both A? and tau, including specific U1 snRNPs, may have potential mechanistic roles in linking A? plaques to tau tangle pathology during AD progression.

SUBMITTER: Hales CM 

PROVIDER: S-EPMC5462625 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature